rs727503227
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001145809.2(MYH14):c.4441C>T(p.Arg1481Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,611,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1481H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001145809.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.4441C>T | p.Arg1481Cys | missense_variant | 33/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.4342C>T | p.Arg1448Cys | missense_variant | 32/42 | ||
MYH14 | NM_024729.4 | c.4318C>T | p.Arg1440Cys | missense_variant | 31/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.4441C>T | p.Arg1481Cys | missense_variant | 33/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000292 AC: 7AN: 239332Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131786
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1459592Hom.: 0 Cov.: 32 AF XY: 0.0000331 AC XY: 24AN XY: 726130
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 07, 2014 | The Arg1481Cys variant in MYH14 has not been reported in individuals with hearin g loss and data from large population studies is insufficient to assess the freq uency of this variant. Computational analyses (biochemical amino acid properties , conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support fo r or against an impact to the protein. In summary, additional information is nee ded to determine the clinical significance of this variant. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at