rs139638446
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM5BP6_Very_StrongBS2
The NM_006514.4(SCN10A):āc.3674T>Cā(p.Ile1225Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,614,116 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1225L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.3674T>C | p.Ile1225Thr | missense_variant | 21/28 | ENST00000449082.3 | NP_006505.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.3674T>C | p.Ile1225Thr | missense_variant | 21/28 | 1 | NM_006514.4 | ENSP00000390600 | P4 | |
SCN10A | ENST00000655275.1 | c.3698T>C | p.Ile1233Thr | missense_variant | 21/28 | ENSP00000499510 | ||||
SCN10A | ENST00000643924.1 | c.3671T>C | p.Ile1224Thr | missense_variant | 20/27 | ENSP00000495595 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000460 AC: 70AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000569 AC: 143AN: 251354Hom.: 1 AF XY: 0.000633 AC XY: 86AN XY: 135828
GnomAD4 exome AF: 0.000493 AC: 720AN: 1461808Hom.: 3 Cov.: 31 AF XY: 0.000534 AC XY: 388AN XY: 727196
GnomAD4 genome AF: 0.000460 AC: 70AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.000470 AC XY: 35AN XY: 74468
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 05, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | SCN10A: BS1 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 05, 2017 | 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. - |
Brugada syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | Aug 22, 2023 | - - |
SCN10A-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 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). - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2018 | 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