11-77203155-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000260.4(MYO7A):c.5264C>T(p.Ala1755Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000509 in 1,551,178 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1755T) has been classified as Likely benign.
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.5264C>T | p.Ala1755Val | missense_variant | 38/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.5264C>T | p.Ala1755Val | missense_variant | 38/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000115 AC: 18AN: 156170Hom.: 0 AF XY: 0.000120 AC XY: 10AN XY: 83172
GnomAD4 exome AF: 0.0000529 AC: 74AN: 1398824Hom.: 0 Cov.: 31 AF XY: 0.0000623 AC XY: 43AN XY: 690194
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74502
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 05, 2022 | In silico analysis supports a deleterious effect on splicing; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter 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 | Aug 26, 2015 | The p.Ala1755Val variant in MYO7A has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 3/7904 South A sian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org). Splice prediction tools suggest the creation of a cryptic 5' splice site; however, this information is not predictive enough to determine pathogeni city. Additional computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ala1755Val variant is uncertain. - |
Usher syndrome type 1B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
MYO7A-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 23, 2023 | The MYO7A c.5264C>T variant is predicted to result in the amino acid substitution p.Ala1755Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-76914200-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at