Variant 2-166405765-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM4BP6_Moderate

The NM_002976.4(SCN7A):c.4864C>T(p.Arg1622Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,612,834 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 6 hom. )

Consequence

SCN7A
NM_002976.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.34

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 Uncertain_significance. Variant got 0 ACMG points.

PM4

Stoplost variant in NM_002976.4 Downstream stopcodon found after 5 codons.

BP6

Variant 2-166405765-G-A is Benign according to our data. Variant chr2-166405765-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 747563.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.4864C>T	p.Arg1622Ter	stop_gained	26/26	ENST00000643258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCN7A	ENST00000643258.1 linkuse as main transcript	c.4864C>T	p.Arg1622Ter	stop_gained	26/26		NM_002976.4	P1
SCN7A	ENST00000441411.2 linkuse as main transcript	c.4864C>T	p.Arg1622Ter	stop_gained	25/25	1		P1
SCN7A	ENST00000424326.5 linkuse as main transcript	c.*2669C>T		3_prime_UTR_variant, NMD_transcript_variant	26/26	1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000396

AC:

AN:

247594

Hom.:

AF XY:

0.000581

AC XY:

AN XY:

134302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00301

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000209

AC:

305

AN:

1460764

Hom.:

Cov.:

AF XY:

0.000307

AC XY:

223

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00317

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000102

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000397

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

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

Oct 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.60

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.94

MutationTaster

Benign

1.0

Vest4

0.81

GERP RS

2.6

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