rs146633221
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_016239.4(MYO15A):c.6112C>T(p.Arg2038Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000377 in 1,610,906 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2038H) has been classified as Uncertain significance.
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.6112C>T | p.Arg2038Cys | missense_variant | 28/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.6112C>T | p.Arg2038Cys | missense_variant | 28/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000394 AC: 60AN: 152232Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000445 AC: 108AN: 242794Hom.: 0 AF XY: 0.000493 AC XY: 65AN XY: 131936
GnomAD4 exome AF: 0.000376 AC: 548AN: 1458556Hom.: 2 Cov.: 35 AF XY: 0.000381 AC XY: 276AN XY: 725156
GnomAD4 genome AF: 0.000394 AC: 60AN: 152350Hom.: 1 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74500
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 31, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | MYO15A: BP4 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 29, 2013 | Arg2038Cys in Exon 28 of MYO15A: This variant is not expected to have clinical s ignificance because it has been identified in 0.2% (14/7692) of Latino chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs146633221), and the Arginine (Arg) at position 2038 is not conserved in ma mmals or evolutionarily distant species and the change to Cysteine (Cys) is pres ent in several species including rat and mouse. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at