rs370538243
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM1BP4_ModerateBP6_Very_Strong
The NM_000256.3(MYBPC3):c.1370C>T(p.Thr457Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,611,942 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T457A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000256.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.1370C>T | p.Thr457Met | missense_variant | 16/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.1370C>T | p.Thr457Met | missense_variant | 16/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.1370C>T | p.Thr457Met | missense_variant | 15/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.1370C>T | p.Thr457Met | missense_variant, NMD_transcript_variant | 16/27 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000200 AC: 49AN: 245016Hom.: 0 AF XY: 0.000271 AC XY: 36AN XY: 132978
GnomAD4 exome AF: 0.000114 AC: 167AN: 1459710Hom.: 1 Cov.: 31 AF XY: 0.000157 AC XY: 114AN XY: 726004
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74382
ClinVar
Submissions by phenotype
Cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Dec 01, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 10, 2021 | - - |
Primary familial hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, no assertion criteria provided | research | CSER _CC_NCGL, University of Washington | Jun 01, 2014 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 08, 2022 | 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