chr2-166406121-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002976.4(SCN7A):c.4508C>T(p.Ser1503Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000596 in 1,611,582 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00030 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 19 hom. )
Consequence
SCN7A
NM_002976.4 missense
NM_002976.4 missense
Scores
1
6
7
Clinical Significance
Conservation
PhyloP100: 2.81
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.025952637).
BP6
?
Variant 2-166406121-G-A is Benign according to our data. Variant chr2-166406121-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3055155.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000628 (916/1459700) while in subpopulation EAS AF= 0.0218 (863/39624). AF 95% confidence interval is 0.0206. There are 19 homozygotes in gnomad4_exome. There are 432 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN7A | NM_002976.4 | c.4508C>T | p.Ser1503Phe | missense_variant | 26/26 | ENST00000643258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN7A | ENST00000643258.1 | c.4508C>T | p.Ser1503Phe | missense_variant | 26/26 | NM_002976.4 | P1 | ||
SCN7A | ENST00000441411.2 | c.4508C>T | p.Ser1503Phe | missense_variant | 25/25 | 1 | P1 | ||
SCN7A | ENST00000424326.5 | c.*2313C>T | 3_prime_UTR_variant, NMD_transcript_variant | 26/26 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000297 AC: 45AN: 151764Hom.: 2 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
45
AN:
151764
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000184 AC: 45AN: 244778Hom.: 0 AF XY: 0.000158 AC XY: 21AN XY: 132900
GnomAD3 exomes
AF:
AC:
45
AN:
244778
Hom.:
AF XY:
AC XY:
21
AN XY:
132900
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000628 AC: 916AN: 1459700Hom.: 19 Cov.: 32 AF XY: 0.000595 AC XY: 432AN XY: 726060
GnomAD4 exome
AF:
AC:
916
AN:
1459700
Hom.:
Cov.:
32
AF XY:
AC XY:
432
AN XY:
726060
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000296 AC: 45AN: 151882Hom.: 2 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74238
GnomAD4 genome
?
AF:
AC:
45
AN:
151882
Hom.:
Cov.:
32
AF XY:
AC XY:
22
AN XY:
74238
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
24
Asia WGS
AF:
AC:
5
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SCN7A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 08, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;M;M
MutationTaster
Benign
D
PrimateAI
Benign
T
Sift4G
Pathogenic
D;D;D;.;.
Polyphen
B;B;B;B;B
Vest4
MVP
MPC
0.038
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at