Variant chr3-38697672-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006514.4(SCN10A):c.5548C>G(p.Gln1850Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SCN10A
NM_006514.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 4.80

Variant links:

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]

SCN10A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN10A	NM_006514.4 linkuse as main transcript	c.5548C>G	p.Gln1850Glu	missense_variant	28/28	ENST00000449082.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCN10A	ENST00000449082.3 linkuse as main transcript	c.5548C>G	p.Gln1850Glu	missense_variant	28/28	1	NM_006514.4	P4
SCN10A	ENST00000655275.1 linkuse as main transcript	c.5572C>G	p.Gln1858Glu	missense_variant	28/28
SCN10A	ENST00000643924.1 linkuse as main transcript	c.5545C>G	p.Gln1849Glu	missense_variant	27/27			A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727246

show subpopulations

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:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brugada syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 03, 2023

This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1850 of the SCN10A protein (p.Gln1850Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1163442). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Aug 13, 2020

- -

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The p.Q1850E variant (also known as c.5548C>G), located in coding exon 27 of the SCN10A gene, results from a C to G substitution at nucleotide position 5548. The glutamine at codon 1850 is replaced by glutamic acid, an amino acid with highly similar 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

0.10

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;.;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

.;D;D;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.43

T;T;T;T

MetaSVM

Pathogenic

0.90

MutationAssessor

Benign

2.0

M;.;M;.

MutationTaster

Benign

0.84

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.4

N;.;.;.

REVEL

Uncertain

0.49

Sift

Benign

0.14

T;.;.;.

Sift4G

Benign

0.27

T;.;.;.

Polyphen

0.96

D;.;D;.

Vest4

0.23

MutPred

0.39

Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);Loss of helix (P = 0.0123);.;

MVP

0.94

MPC

0.073

ClinPred

0.77

GERP RS

5.3

Varity_R

0.24

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over