rs7595255

Variant names:

• chr2-166226468-T-A
• rs7595255
• NM_001365536.1:c.4398+99A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166226468-T-A
• chr2-166226468-T-C
• chr2-166226468-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365536.1(SCN9A):​c.4398+99A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 636,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 5 publications found

Genes affected

SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.4398+99A>T		intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.4365+99A>T		intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.612-21727T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.4398+99A>T		intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.4398+99A>T		intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.4365+99A>T		intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000157 AC: 1 AN: 636906 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 324724

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14920

American (AMR) AF: 0.00 AC: 0 AN: 16620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15004

East Asian (EAS) AF: 0.00 AC: 0 AN: 29350

South Asian (SAS) AF: 0.00 AC: 0 AN: 37090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2326

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 447708

Other (OTH) AF: 0.0000322 AC: 1 AN: 31080

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.28
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7595255; hg19: chr2-167082978;