NM_006514.4:c.5810C>G

Variant names:

• chr3-38697410-G-C
• NM_006514.4:c.5810C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006514.4(SCN10A):​c.5810C>G​(p.Ser1937Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN10A NM_006514.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27831697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.5810C>G	p.Ser1937Cys	missense_variant	Exon 28 of 28	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.5810C>G	p.Ser1937Cys	missense_variant	Exon 28 of 28	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.5807C>G	p.Ser1936Cys	missense_variant	Exon 27 of 27			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.5834C>G	p.Ser1945Cys	missense_variant	Exon 28 of 28			ENSP00000499510.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Uncertain:1

Dec 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.S1937C variant (also known as c.5810C>G), located in coding exon 27 of the SCN10A gene, results from a C to G substitution at nucleotide position 5810. The serine at codon 1937 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;.;T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	.;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	0.0	N;.;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D;.;.;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D;.;.;.
Sift4G	Uncertain	0.0050	D;.;.;.
Polyphen		1.0	D;.;D;.
Vest4		0.30
MutPred		0.25		Gain of glycosylation at S1937 (P = 0.0193);Gain of glycosylation at S1937 (P = 0.0193);Gain of glycosylation at S1937 (P = 0.0193);.;
MVP		0.93
MPC		0.34
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.40
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38738901;