rs117612144
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_016239.4(MYO15A):c.3026C>A(p.Pro1009His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,612,882 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.3026C>A | p.Pro1009His | missense_variant | 2/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.3026C>A | p.Pro1009His | missense_variant | 2/66 | NM_016239.4 | P1 | ||
MYO15A | ENST00000583079.1 | n.2659C>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.00373 AC: 567AN: 152188Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.00591 AC: 1466AN: 247930Hom.: 26 AF XY: 0.00568 AC XY: 767AN XY: 135008
GnomAD4 exome AF: 0.00329 AC: 4807AN: 1460576Hom.: 67 Cov.: 44 AF XY: 0.00327 AC XY: 2374AN XY: 726574
GnomAD4 genome ? AF: 0.00373 AC: 568AN: 152306Hom.: 2 Cov.: 33 AF XY: 0.00459 AC XY: 342AN XY: 74464
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 30, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | MYO15A: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Autosomal recessive nonsyndromic hearing loss 3 Pathogenic:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Pathogenic, flagged submission | clinical testing | Molecular Diagnosis Center for Deafness | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 12, 2015 | p.Pro1009His in exon 2 of MYO15A: This variant was reported as homozygous in one Chinese (Hans) individual with hearing loss (Yang 2013); however, it is not e xpected to have clinical significance because it has been identified in 4.6% (39 5/8578) of East Asian chromosomes, including 14 homozygous individuals, by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs11761 2144). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at