rs183969516
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016239.4(MYO15A):c.823G>A(p.Gly275Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. 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. G275R) has been classified as Likely benign.
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.823G>A | p.Gly275Ser | missense_variant | 2/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.823G>A | p.Gly275Ser | missense_variant | 2/66 | NM_016239.4 | P1 | ||
MYO15A | ENST00000583079.1 | n.456G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000167 AC: 4AN: 239140Hom.: 0 AF XY: 0.00000762 AC XY: 1AN XY: 131316
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1450890Hom.: 0 Cov.: 36 AF XY: 0.00000277 AC XY: 2AN XY: 722258
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 13, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 10, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 275 of the MYO15A protein (p.Gly275Ser). This variant is present in population databases (rs183969516, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYO15A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1031961). 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 MYO15A protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at