rs376303259

Variant names:

• chr2-166277033-C-A
• NM_001365536.1:c.2824G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166277033-C-A
• chr2-166277033-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365536.1(SCN9A):​c.2824G>T​(p.Ala942Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15323952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.2824G>T	p.Ala942Ser	missense_variant	Exon 16 of 27	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.2824G>T	p.Ala942Ser	missense_variant	Exon 16 of 27		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.2824G>T	p.Ala942Ser	missense_variant	Exon 16 of 27	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.2791G>T	p.Ala931Ser	missense_variant	Exon 16 of 27	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.2791G>T	p.Ala931Ser	missense_variant	Exon 16 of 27			ENSP00000495983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461786 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.77
DEOGEN2	Benign	0.42	.;T;.;.;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.61	T;.;T;T;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.0085	D
MutationAssessor	Benign	-0.11	.;N;.;.;N;N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.67	N;.;.;.;.;N;.
REVEL	Uncertain	0.30
Sift	Benign	0.46	T;.;.;.;.;T;.
Sift4G	Benign	0.82	T;T;.;.;.;T;.
Vest4		0.13
MutPred		0.73		Loss of catalytic residue at A931 (P = 0.1233);.;Loss of catalytic residue at A931 (P = 0.1233);Loss of catalytic residue at A931 (P = 0.1233);.;.;.;
MVP		0.41
MPC		0.12
ClinPred		0.033	T
GERP RS		-2.3
Varity_R		0.093
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-167133543;