chr19-50309767-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001145809.2(MYH14):c.6088T>A(p.Ser2030Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,419,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. S2030A) has been classified as Likely benign.
Frequency
Consequence
NM_001145809.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.6088T>A | p.Ser2030Thr | missense_variant | 43/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.5989T>A | p.Ser1997Thr | missense_variant | 42/42 | ||
MYH14 | NM_024729.4 | c.5965T>A | p.Ser1989Thr | missense_variant | 41/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.6088T>A | p.Ser2030Thr | missense_variant | 43/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 exomes AF: 0.00000502 AC: 1AN: 199316Hom.: 0 AF XY: 0.00000929 AC XY: 1AN XY: 107618
GnomAD4 exome AF: 7.04e-7 AC: 1AN: 1419508Hom.: 0 Cov.: 35 AF XY: 0.00000142 AC XY: 1AN XY: 703836
GnomAD4 genome Cov.: 30
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 | Dec 12, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Ser2030Thr vari ant in MYH14 has not been previously reported in individuals with hearing loss o r in large population studies. Computational analyses (biochemical amino acid pr operties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ser2030 Thr variant may not impact the protein, though this information is not predictiv e enough to rule out pathogenicity. In summary, the clinical significance of thi s variant cannot be determined with certainty; however based upon the conservati on and computational data, we would lean towards a more likely benign role. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at