rs143610297

chr3-38723527-C-Gchr3-38723527-C-T

Variant summary

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

The NM_006514.4(SCN10A):c.3255G>C(p.Glu1085Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,250 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. E1085E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SCN10A NM_006514.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=0.37960973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4	c.3255G>C	p.Glu1085Asp	missense_variant	19/28	ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN10A	ENST00000449082.3	c.3255G>C	p.Glu1085Asp	missense_variant	19/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1	c.3279G>C	p.Glu1093Asp	missense_variant	19/28
SCN10A	ENST00000643924.1	c.3252G>C	p.Glu1084Asp	missense_variant	18/27			A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000433 AC: 1 AN: 231182 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 125212

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 SAS exome AF: 0.0000343

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454250 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722916

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: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	13
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;.;D;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.43	N
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Uncertain	-0.061	T
MutationAssessor	Uncertain	2.4	M;.;M;.
MutationTaster	Benign	0.56	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.8	D;.;.;.
REVEL	Uncertain	0.42
Sift	Benign	0.048	D;.;.;.
Sift4G	Benign	0.085	T;.;.;.
Polyphen		0.70	P;.;P;.
Vest4		0.38
MutPred		0.55		Gain of glycosylation at S1082 (P = 0.0122);Gain of glycosylation at S1082 (P = 0.0122);Gain of glycosylation at S1082 (P = 0.0122);.;
MVP		0.61
MPC		0.083
ClinPred		0.88	D
GERP RS		-2.6
Varity_R		0.33
gMVP		0.39

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: rs143610297; hg19: chr3-38765018;