rs781354273

Positions:

• chr3-38739637-C-G
• chr3-38739637-C-T

Variant summary

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

The ENST00000449082.3(SCN10A):​c.2158G>C​(p.Asp720His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D720N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN10A ENST00000449082.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.2158G>C	p.Asp720His	missense_variant	15/28	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.2158G>C	p.Asp720His	missense_variant	15/28	1	NM_006514.4	ENSP00000390600	P4
SCN10A	ENST00000655275.1	c.2185G>C	p.Asp729His	missense_variant	15/28			ENSP00000499510
SCN10A	ENST00000643924.1	c.2158G>C	p.Asp720His	missense_variant	14/27			ENSP00000495595	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.85	D;.;D;.
Eigen	Benign	0.032
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Benign	1.4	L;.;L;.
MutationTaster	Benign	0.96	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.7	D;.;.;.
REVEL	Uncertain	0.59
Sift	Benign	0.073	T;.;.;.
Sift4G	Benign	0.22	T;.;.;.
Polyphen		0.69	P;.;P;.
Vest4		0.46
MutPred		0.63		Loss of ubiquitination at K715 (P = 0.0834);Loss of ubiquitination at K715 (P = 0.0834);Loss of ubiquitination at K715 (P = 0.0834);Loss of ubiquitination at K715 (P = 0.0834);
MVP		0.86
MPC		0.33
ClinPred		0.99	D
GERP RS		2.3
Varity_R		0.39
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -21

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: chr3-38781128;