rs370256265
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001145809.2(MYH14):c.3475G>T(p.Asp1159Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,612,258 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D1159D) has been classified as Likely benign.
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.3475G>T | p.Asp1159Tyr | missense_variant | 28/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.3376G>T | p.Asp1126Tyr | missense_variant | 27/42 | ||
MYH14 | NM_024729.4 | c.3352G>T | p.Asp1118Tyr | missense_variant | 26/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.3475G>T | p.Asp1159Tyr | missense_variant | 28/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000946 AC: 23AN: 243084Hom.: 0 AF XY: 0.000105 AC XY: 14AN XY: 132850
GnomAD4 exome AF: 0.000338 AC: 493AN: 1460038Hom.: 2 Cov.: 32 AF XY: 0.000307 AC XY: 223AN XY: 726214
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74358
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 | Sep 04, 2013 | The Asp1159Tyr variant in MYH14 has not been reported in individuals with hearin g loss, but has been identified in 0.04% (3/8230) of European American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS, dbSN P rs370256265). Although this variant was identified in the general population, its frequency is not high enough to rule out a pathogenic role. Computational an alyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, a nd SIFT) do not provide strong support for or against an impact to the protein. In summary,additional information is needed to fully assess the clinical signifi cance of the Asp1159Tyr variant. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2021 | The c.3352G>T (p.D1118Y) alteration is located in exon 26 (coding exon 25) of the MYH14 gene. This alteration results from a G to T substitution at nucleotide position 3352, causing the aspartic acid (D) at amino acid position 1118 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 04, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; 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