rs58465962

Variant names:

• chr2-166288596-C-A
• rs58465962
• NM_001365536.1:c.1155G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166288596-C-A
• chr2-166288596-C-T

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.1155G>T​(p.Val385Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,611,628 control chromosomes in the GnomAD database, including 754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (389 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (365 hom.)
• Consequence: SCN9A NM_001365536.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.490
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 2-166288596-C-A is Benign according to our data. Variant chr2-166288596-C-A is described in ClinVar as Benign. ClinVar VariationId is 130255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 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.1155G>T	p.Val385Val	synonymous	Exon 10 of 27	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.1155G>T	p.Val385Val	synonymous	Exon 10 of 27	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.1030-5969C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.1155G>T	p.Val385Val	synonymous	Exon 10 of 27	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.1155G>T	p.Val385Val	synonymous	Exon 10 of 27	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.1155G>T	p.Val385Val	synonymous	Exon 10 of 27	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6245 AN: 152052 Hom.: 389 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.0349

GnomAD2 exomes AF: 0.0150 AC: 3726 AN: 248062 AF XY: 0.0138

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.00841

Gnomad ASJ exome AF: 0.0356

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00358

Gnomad OTH exome AF: 0.0131

GnomAD4 exome AF: 0.00765 AC: 11162 AN: 1459460 Hom.: 365 Cov.: 34 AF XY: 0.00776 AC XY: 5633 AN XY: 725944

African (AFR) AF: 0.136 AC: 4540 AN: 33432

American (AMR) AF: 0.0102 AC: 455 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 962 AN: 26052

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.0166 AC: 1425 AN: 85834

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53322

Middle Eastern (MID) AF: 0.0248 AC: 143 AN: 5758

European-Non Finnish (NFE) AF: 0.00239 AC: 2658 AN: 1110428

Other (OTH) AF: 0.0161 AC: 969 AN: 60272

GnomAD4 genome AF: 0.0412 AC: 6268 AN: 152168 Hom.: 389 Cov.: 32 AF XY: 0.0396 AC XY: 2949 AN XY: 74398

African (AFR) AF: 0.132 AC: 5469 AN: 41480

American (AMR) AF: 0.0201 AC: 307 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00347 AC: 236 AN: 68020

Other (OTH) AF: 0.0346 AC: 73 AN: 2110

Alfa AF: 0.0199 Hom.: 84

Bravo AF: 0.0454

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	not provided (3)
-	-	1	Channelopathy-associated congenital insensitivity to pain, autosomal recessive (1)
-	-	1	Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)
-	-	1	Paroxysmal extreme pain disorder (1)
-	-	1	Primary erythromelalgia (1)
-	-	1	Small fiber neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	5.3
DANN	Benign	0.79
PhyloP100		-0.49
Mutation Taster		=81/19	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: rs58465962; hg19: chr2-167145106; COSMIC: COSV104409077;