2-166405701-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002976.4(SCN7A):c.4928G>A(p.Arg1643Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,612,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SCN7A
NM_002976.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

SCN7A (HGNC:10594): (sodium voltage-gated channel alpha subunit 7) This gene encodes one of the many voltage-gated sodium channel proteins. For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer positive charged residues that in other sodium channels; domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. Several alternatively spliced transcript variants exist, but the full-length natures of all of them remain unknown. [provided by RefSeq, Dec 2011]

SCN7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00546962).

BP6

Variant 2-166405701-C-T is Benign according to our data. Variant chr2-166405701-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713051.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN7A	NM_002976.4 linkuse as main transcript	c.4928G>A	p.Arg1643Gln	missense_variant	26/26	ENST00000643258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCN7A	ENST00000643258.1 linkuse as main transcript	c.4928G>A	p.Arg1643Gln	missense_variant	26/26		NM_002976.4	P1
SCN7A	ENST00000441411.2 linkuse as main transcript	c.4928G>A	p.Arg1643Gln	missense_variant	25/25	1		P1
SCN7A	ENST00000424326.5 linkuse as main transcript	c.*2733G>A		3_prime_UTR_variant, NMD_transcript_variant	26/26	1

Frequencies

GnomAD3 genomes

AF:

0.000908

AC:

138

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000213

AC:

AN:

248258

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134696

show subpopulations

Gnomad AFR exome

AF:

0.00304

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000109

AC:

159

AN:

1460846

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.00305

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000907

AC:

138

AN:

152148

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00313

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.00189

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000290

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

Cadd

Benign

9.8

Dann

Benign

0.74

DEOGEN2

Benign

0.31

T;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.051

M_CAP

Benign

0.0079

MetaRNN

Benign

0.0055

T;T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

-0.52

N;N;N;N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

Sift4G

Benign

0.41

T;T;T;.;.

Polyphen

0.0

B;B;B;B;B

Vest4

0.041

MVP

0.62

MPC

0.037

ClinPred

0.0046

GERP RS

-1.4

Varity_R

0.031

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over