rs6432901

Variant names:

• chr2-166311583-C-T
• rs6432901
• NM_001365536.1:c.174G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-166311583-C-T
• chr2-166311583-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001365536.1(SCN9A):​c.174G>A​(p.Gln58Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,612,054 control chromosomes in the GnomAD database, including 313,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31209 hom., cov: 25)
  • Exomes 𝑓: 0.62 (282213 hom.)
• Consequence: SCN9A NM_001365536.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:18
• Conservation: PhyloP100: -0.0820
• Publications: 21 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 2-166311583-C-T is Benign according to our data. Variant chr2-166311583-C-T is described in ClinVar as Benign. ClinVar VariationId is 130259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.082 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

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.174G>A	p.Gln58Gln	synonymous	Exon 2 of 27	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.174G>A	p.Gln58Gln	synonymous	Exon 2 of 27	NP_002968.2	Q15858-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.174G>A	p.Gln58Gln	synonymous	Exon 2 of 27	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.174G>A	p.Gln58Gln	synonymous	Exon 2 of 27	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.174G>A	p.Gln58Gln	synonymous	Exon 2 of 27	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.637 AC: 95890 AN: 150528 Hom.: 31188 Cov.: 25

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.636

GnomAD2 exomes AF: 0.576 AC: 143655 AN: 249532 AF XY: 0.577

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.434

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.633

Gnomad OTH exome AF: 0.585

GnomAD4 exome AF: 0.618 AC: 903294 AN: 1461408 Hom.: 282213 Cov.: 46 AF XY: 0.616 AC XY: 447929 AN XY: 726996

African (AFR) AF: 0.746 AC: 24976 AN: 33472

American (AMR) AF: 0.467 AC: 20876 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 13421 AN: 26126

East Asian (EAS) AF: 0.426 AC: 16909 AN: 39700

South Asian (SAS) AF: 0.542 AC: 46705 AN: 86212

European-Finnish (FIN) AF: 0.541 AC: 28879 AN: 53388

Middle Eastern (MID) AF: 0.548 AC: 3157 AN: 5764

European-Non Finnish (NFE) AF: 0.640 AC: 711325 AN: 1111670

Other (OTH) AF: 0.614 AC: 37046 AN: 60358

GnomAD4 genome AF: 0.637 AC: 95952 AN: 150646 Hom.: 31209 Cov.: 25 AF XY: 0.628 AC XY: 46177 AN XY: 73484

African (AFR) AF: 0.749 AC: 30721 AN: 41016

American (AMR) AF: 0.552 AC: 8341 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1749 AN: 3456

East Asian (EAS) AF: 0.424 AC: 2130 AN: 5022

South Asian (SAS) AF: 0.546 AC: 2596 AN: 4758

European-Finnish (FIN) AF: 0.532 AC: 5506 AN: 10342

Middle Eastern (MID) AF: 0.559 AC: 162 AN: 290

European-Non Finnish (NFE) AF: 0.633 AC: 42837 AN: 67658

Other (OTH) AF: 0.632 AC: 1318 AN: 2086

Alfa AF: 0.633 Hom.: 67378

Bravo AF: 0.640

Asia WGS AF: 0.498 AC: 1734 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	3	not provided (3)
-	-	2	Channelopathy-associated congenital insensitivity to pain, autosomal recessive (2)
-	-	2	Paroxysmal extreme pain disorder (2)
-	-	2	Primary erythromelalgia (2)
-	-	1	Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)
-	-	1	Small fiber neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.8
DANN	Benign	0.67
PhyloP100		-0.082
Mutation Taster		=100/0	polymorphism (auto)

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: rs6432901; hg19: chr2-167168093; COSMIC: COSV57601199;