rs200014315

Variant names:

• chr2-166281803-C-A
• rs200014315
• NM_001365536.1:c.1980G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166281803-C-A
• chr2-166281803-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001365536.1(SCN9A):​c.1980G>T​(p.Thr660Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,762 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. Synonymous variant affecting the same amino acid position (i.e. T660T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SCN9A NM_001365536.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 2 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-0.337 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.1980G>T	p.Thr660Thr	synonymous	Exon 13 of 27	NP_001352465.1
	SCN9A	NM_002977.4		c.1947G>T	p.Thr649Thr	synonymous	Exon 13 of 27	NP_002968.2
	SCN1A-AS1	NR_110260.1		n.1029+4556C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.1980G>T	p.Thr660Thr	synonymous	Exon 13 of 27	ENSP00000495601.1
	SCN9A	ENST00000303354.11	TSL:5	c.1980G>T	p.Thr660Thr	synonymous	Exon 13 of 27	ENSP00000304748.7
	SCN9A	ENST00000409672.5	TSL:5	c.1947G>T	p.Thr649Thr	synonymous	Exon 13 of 27	ENSP00000386306.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000861 AC: 2 AN: 232338 AF XY: 0.0000159

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449762 Hom.: 0 Cov.: 30 AF XY: 0.00000416 AC XY: 3 AN XY: 720946

⚠️ 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: 32586

American (AMR) AF: 0.00 AC: 0 AN: 41996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25560

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108104

Other (OTH) AF: 0.00 AC: 0 AN: 59848

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0225104), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.86
DANN	Benign	0.62
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200014315; hg19: chr2-167138313;