chr19-50281696-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001145809.2(MYH14):c.4393C>T(p.Arg1465Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,611,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1465H) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.4393C>T | p.Arg1465Cys | missense_variant | 33/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.4294C>T | p.Arg1432Cys | missense_variant | 32/42 | ||
MYH14 | NM_024729.4 | c.4270C>T | p.Arg1424Cys | missense_variant | 31/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.4393C>T | p.Arg1465Cys | missense_variant | 33/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000666 AC: 16AN: 240414Hom.: 0 AF XY: 0.0000379 AC XY: 5AN XY: 132030
GnomAD4 exome AF: 0.000123 AC: 180AN: 1459674Hom.: 0 Cov.: 32 AF XY: 0.000103 AC XY: 75AN XY: 726164
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74378
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The MYH14 p.Arg1432Cys variant was not identified in the literature but was identified in dbSNP (ID: rs727505272) and ClinVar (classified as uncertain significance by Laboratory for Molecular Medicine). The variant was identified in control databases in 17 of 271800 chromosomes at a frequency of 0.00006255 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 16 of 122392 chromosomes (freq: 0.000131) and African in 1 of 22862 chromosomes (freq: 0.000044), but was not observed in the Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Arg1432 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 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 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 02, 2014 | The Arg1465Cys variant in MYH14 gene has not been previously reported in individ uals with hearing loss. Data from large population studies is insufficient to as sess the frequency of this variant. Computational prediction tools and conservat ion analyses do not provide strong support for or against an impact to the prote in. In summary, the clinical significance of the Arg1465Cys variant is uncertain . - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at