rs13414203

Variant names:

• chr2-166288632-A-G
• rs13414203
• NM_001365536.1:c.1119T>C

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.1119T>C​(p.Ala373Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,588,578 control chromosomes in the GnomAD database, including 119,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11116 hom., cov: 31)
  • Exomes 𝑓: 0.39 (108323 hom.)
• Consequence: SCN9A NM_001365536.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 1.08
• 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=-0.41).
• BP6: Variant 2-166288632-A-G is Benign according to our data. Variant chr2-166288632-A-G is described in ClinVar as Benign. ClinVar VariationId is 130254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 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.1119T>C	p.Ala373Ala	synonymous	Exon 10 of 27	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.1119T>C	p.Ala373Ala	synonymous	Exon 10 of 27	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.1030-5933A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.1119T>C	p.Ala373Ala	synonymous	Exon 10 of 27	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.1119T>C	p.Ala373Ala	synonymous	Exon 10 of 27	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.1119T>C	p.Ala373Ala	synonymous	Exon 10 of 27	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57848 AN: 151844 Hom.: 11120 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.367 AC: 88292 AN: 240754 AF XY: 0.368

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.316

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.386 AC: 554591 AN: 1436616 Hom.: 108323 Cov.: 34 AF XY: 0.385 AC XY: 274355 AN XY: 712816

African (AFR) AF: 0.376 AC: 12326 AN: 32772

American (AMR) AF: 0.279 AC: 12056 AN: 43192

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 8972 AN: 25372

East Asian (EAS) AF: 0.306 AC: 12064 AN: 39422

South Asian (SAS) AF: 0.355 AC: 29127 AN: 82080

European-Finnish (FIN) AF: 0.417 AC: 21948 AN: 52688

Middle Eastern (MID) AF: 0.305 AC: 1721 AN: 5644

European-Non Finnish (NFE) AF: 0.396 AC: 433924 AN: 1096214

Other (OTH) AF: 0.379 AC: 22453 AN: 59232

GnomAD4 genome AF: 0.381 AC: 57869 AN: 151962 Hom.: 11116 Cov.: 31 AF XY: 0.378 AC XY: 28043 AN XY: 74282

African (AFR) AF: 0.379 AC: 15726 AN: 41454

American (AMR) AF: 0.318 AC: 4842 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1235 AN: 3468

East Asian (EAS) AF: 0.310 AC: 1597 AN: 5146

South Asian (SAS) AF: 0.356 AC: 1716 AN: 4814

European-Finnish (FIN) AF: 0.414 AC: 4367 AN: 10556

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27379 AN: 67972

Other (OTH) AF: 0.367 AC: 773 AN: 2108

Alfa AF: 0.389 Hom.: 9771

Bravo AF: 0.372

Asia WGS AF: 0.352 AC: 1231 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	Inherited Erythromelalgia (1)
-	-	1	Paroxysmal extreme pain disorder (1)
-	-	1	Primary erythromelalgia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		1.1
Mutation Taster		=94/6	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: rs13414203; hg19: chr2-167145142; COSMIC: COSV57621345;