rs771755654
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP5BP4BS1_SupportingBS2
The NM_001145809.2(MYH14):c.4297G>A(p.Glu1433Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,586,656 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 Conflicting classifications of pathogenicity (no stars).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.4297G>A | p.Glu1433Lys | missense_variant | Exon 33 of 43 | ENST00000642316.2 | NP_001139281.1 | |
MYH14 | NM_001077186.2 | c.4198G>A | p.Glu1400Lys | missense_variant | Exon 32 of 42 | NP_001070654.1 | ||
MYH14 | NM_024729.4 | c.4174G>A | p.Glu1392Lys | missense_variant | Exon 31 of 41 | NP_079005.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000399 AC: 9AN: 225824Hom.: 0 AF XY: 0.0000485 AC XY: 6AN XY: 123798
GnomAD4 exome AF: 0.0000328 AC: 47AN: 1434450Hom.: 0 Cov.: 32 AF XY: 0.0000352 AC XY: 25AN XY: 710278
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74354
ClinVar
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 4A Pathogenic:1
A very rare variant predicted to cause damage by most prediction programs. -
not specified Uncertain:1
The p.Glu1433Lys variant in MYH14 has not been previously reported in individual s with hearing loss, but has been identified in 3/59206 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 771755654). Although this variant has been seen in the general population, its f requency is not high enough to rule out a pathogenic role. Computational predict ion tools and conservation analyses suggest that the p.Glu1433Lys variant may im pact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Glu1433Lys variant is uncertain. -
not provided Uncertain:1
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