rs369539923
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000260.4(MYO7A):c.3038C>T(p.Thr1013Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,613,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1013T) has been classified as Likely benign.
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.3038C>T | p.Thr1013Ile | missense_variant | 24/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.3038C>T | p.Thr1013Ile | missense_variant | 24/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152140Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248500Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135102
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461124Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 726844
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152258Hom.: 0 Cov.: 31 AF XY: 0.000202 AC XY: 15AN XY: 74440
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 15, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 20, 2019 | 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 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 04, 2016 | The p.Thr1013Ile variant in MYO7A has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 6/9716 of Afri can chromosomes and by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs369539923). Although this variant has been seen in the ge neral population, its frequency is not high enough to rule out a pathogenic role . Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical signi ficance of the p.Thr1013Ile variant is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.3038C>T (p.T1013I) alteration is located in exon 24 (coding exon 23) of the MYO7A gene. This alteration results from a C to T substitution at nucleotide position 3038, causing the threonine (T) at amino acid position 1013 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Usher syndrome type 1B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at