Introduction to Variant Nomenclature

How are variants described?

Based on its position in the genome, or based on its position within a specific gene

In the variant NC_000017.11:g.7578263G>A, what does the 17 indicate?

Variant is present on chromosome 17

In the variant NC_000017.11:g.7578263G>A, what does the “g” indicate?

A genomic reference sequence

In the variant NC_000017.11:g.7578263G>A, what does the 7578263G>A indicate?

At position 7,578,263 along chromosome 17, a variant has been identified that substitutes G to A

In the variant, NM_000546.6(TP53):c.586C>T, what does the NM_000546.6(TP53) indicate?

TP53 reference transcript sequence being used, along with the gene name

In the variant, NM_000546.6(TP53):c.586C>T, what “c” indicate?

A coding DNA reference sequence

In the variant, NM_000546.6(TP53):c.586C>T, what does the 586C>T indicate?

At position 586 within the coding region of the TP53 gene, a variant has been identified that substitutes C to T

For variants located outside of mRNA coding sequences, what must be used?

Genomic DNA references

How are protein-coding sequences numbered?

Sequentially from the A in the ATG start codon to the last nucleotide of the stop codon

When it comes to introns, how are nucleotides in the 5’ half numbered?

The last nucleotide of immediate upstream exon, then “+”, then position within intron

When it comes to introns, how are nucleotides in the 3’ half numbered?

From first nucleotide of immediate downstream exon, then “-”, then position within intron

How are 5’UTR nucleotides numbered?

Upstream of start codon ATG, c.-1, c.-2, etc.

How are 3’UTR nucleotides numbered?

Downstream of stop codon, c.*1, c.*2, etc.

What does the nomenclature: NM_000546.6(TP53):c.951_954del mean?

Deletion of four nucleotides from c.951 up to and including c.954

What does nomenclature NM_000546.6(TP53):c.993+2T>C mean?

An intron begins (5’ end) directly downstream of nucleotide c.993. In this intron, at nucleotide position +2 relative to the 5’ end, there is a substitution of T to C

What does nomenclature NM_000546.6(TP53):c.1101-2A>G mean?

An intron ends (3’ end) directly upstream of nucleotide c.1101. In this intron, at nucleotide position -2 relative to the 3’ end, there is a substitution of A to G