3-38726809-T-G

Position:

• chr3-38726809-T-G

Variant summary

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

The ENST00000449082.3(SCN10A):​c.2884A>C​(p.Ile962Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I962V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCN10A ENST00000449082.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434

Genes affected

SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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=0.06953281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.2884A>C	p.Ile962Leu	missense_variant	17/28	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.2884A>C	p.Ile962Leu	missense_variant	17/28	1	NM_006514.4	ENSP00000390600	P4
SCN10A	ENST00000655275.1	c.2911A>C	p.Ile971Leu	missense_variant	17/28			ENSP00000499510
SCN10A	ENST00000643924.1	c.2884A>C	p.Ile962Leu	missense_variant	16/27			ENSP00000495595	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.4
DANN	Benign	0.82
DEOGEN2	Benign	0.042	T;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.24	.;T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.90	L;.;L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.26	N;.;.;.
REVEL	Benign	0.21
Sift	Benign	0.35	T;.;.;.
Sift4G	Benign	0.91	T;.;.;.
Polyphen		0.44	B;.;B;.
Vest4		0.25
MutPred		0.49		Gain of glycosylation at T966 (P = 0.1253);Gain of glycosylation at T966 (P = 0.1253);Gain of glycosylation at T966 (P = 0.1253);Gain of glycosylation at T966 (P = 0.1253);
MVP		0.38
MPC		0.061
ClinPred		0.30	T
GERP RS		-4.2
Varity_R		0.057
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs57326399; hg19: chr3-38768300;