rs867587467
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP5_Moderate
The NM_000334.4(SCN4A):c.692C>T(p.Thr231Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000782 in 1,407,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000078 ( 0 hom. )
Consequence
SCN4A
NM_000334.4 missense
NM_000334.4 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
SCN4A (HGNC:10591): (sodium voltage-gated channel alpha subunit 4) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. It is expressed in skeletal muscle, and mutations in this gene have been linked to several myotonia and periodic paralysis disorders. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a transmembrane_region Helical; Name=S4 of repeat I (size 16) in uniprot entity SCN4A_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_000334.4
PP5
Variant 17-63971173-G-A is Pathogenic according to our data. Variant chr17-63971173-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521304.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN4A | NM_000334.4 | c.692C>T | p.Thr231Met | missense_variant | 5/24 | ENST00000435607.3 | NP_000325.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN4A | ENST00000435607.3 | c.692C>T | p.Thr231Met | missense_variant | 5/24 | 1 | NM_000334.4 | ENSP00000396320 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000117 AC: 2AN: 170542Hom.: 0 AF XY: 0.0000110 AC XY: 1AN XY: 90752
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GnomAD4 exome AF: 0.00000782 AC: 11AN: 1407066Hom.: 0 Cov.: 33 AF XY: 0.00000720 AC XY: 5AN XY: 694910
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GnomAD4 genome Cov.: 32
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32
Bravo
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K228 (P = 0.0704);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at