rs73062575
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006514.4(SCN10A):c.3133C>A(p.Pro1045Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,600,220 control chromosomes in the GnomAD database, including 653 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.3133C>A | p.Pro1045Thr | missense_variant | 18/28 | ENST00000449082.3 | NP_006505.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.3133C>A | p.Pro1045Thr | missense_variant | 18/28 | 1 | NM_006514.4 | ENSP00000390600.2 | ||
SCN10A | ENST00000643924.1 | c.3130C>A | p.Pro1044Thr | missense_variant | 17/27 | ENSP00000495595.1 | ||||
SCN10A | ENST00000655275.1 | c.3157C>A | p.Pro1053Thr | missense_variant | 18/28 | ENSP00000499510.1 |
Frequencies
GnomAD3 genomes AF: 0.0173 AC: 2635AN: 152208Hom.: 25 Cov.: 33
GnomAD3 exomes AF: 0.0155 AC: 3853AN: 248330Hom.: 30 AF XY: 0.0153 AC XY: 2059AN XY: 134212
GnomAD4 exome AF: 0.0259 AC: 37530AN: 1447894Hom.: 628 Cov.: 33 AF XY: 0.0253 AC XY: 18168AN XY: 719370
GnomAD4 genome AF: 0.0173 AC: 2636AN: 152326Hom.: 25 Cov.: 33 AF XY: 0.0156 AC XY: 1160AN XY: 74490
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 12, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 21, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Brugada syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2018 | This alteration is classified as 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