rs201321140
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000260.4(MYO7A):c.4844C>T(p.Pro1615Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000648 in 1,588,930 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P1615P) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.4844C>T | p.Pro1615Leu | missense_variant | 35/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.4844C>T | p.Pro1615Leu | missense_variant | 35/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000295 AC: 7AN: 237558Hom.: 0 AF XY: 0.0000233 AC XY: 3AN XY: 128598
GnomAD4 exome AF: 0.0000654 AC: 94AN: 1436748Hom.: 0 Cov.: 33 AF XY: 0.0000648 AC XY: 46AN XY: 710166
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 12, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1615 of the MYO7A protein (p.Pro1615Leu). This variant is present in population databases (rs201321140, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 229006). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYO7A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 03, 2015 | The p.Pro1615Leu variant in MYO7A has not been previously reported in individual s with hearing loss, but has been identified in 2/62452 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 201321140). Computational prediction tools and conservation analyses suggest the variant may not impact the protein, though this information is not predictive e nough to rule out pathogenicity. In summary, the clinical significance of the p .Pro1615Leu variant is uncertain. - |
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jun 09, 2017 | - - |
Usher syndrome type 1B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 21, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at