rs375458594
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_006514.4(SCN10A):āc.4063A>Gā(p.Met1355Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā ā ).
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.4063A>G | p.Met1355Val | missense_variant | 23/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.4063A>G | p.Met1355Val | missense_variant | 23/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.4087A>G | p.Met1363Val | missense_variant | 23/28 | ||||
SCN10A | ENST00000643924.1 | c.4060A>G | p.Met1354Val | missense_variant | 22/27 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251292Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135792
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727230
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74356
ClinVar
Submissions by phenotype
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 18, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at