14-23390342-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_002471.4(MYH6):āc.3447C>Gā(p.Ser1149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,608,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002471.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3447C>G | p.Ser1149Arg | missense_variant | Exon 26 of 39 | ENST00000405093.9 | NP_002462.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000528 AC: 8AN: 151420Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000915 AC: 22AN: 240372Hom.: 0 AF XY: 0.000114 AC XY: 15AN XY: 131608
GnomAD4 exome AF: 0.0000453 AC: 66AN: 1456718Hom.: 0 Cov.: 34 AF XY: 0.0000497 AC XY: 36AN XY: 724734
GnomAD4 genome AF: 0.0000528 AC: 8AN: 151534Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 74024
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Ser1149Arg variant in MYH6 has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.10% (10/9638) of Ashkenazi Je wish chromosomes by the genome Aggregation Database (gnomAD, http://gnomad.broad institute.org/; dbSNP rs564367705). Computational prediction tools and conservat ion analysis suggest that the p.Ser1149Arg variant may impact the protein, thoug h this information is not predictive enough to determine pathogenicity. In summa ry, the clinical significance of the p.Ser1149Arg variant is uncertain. -
Hypertrophic cardiomyopathy 14 Benign:1
- -
Cardiomyopathy Benign:1
- -
Cardiovascular phenotype Benign:1
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