15-52376435-G-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001382347.1(MYO5A):c.2332C>T(p.Arg778Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000186 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MYO5A
NM_001382347.1 stop_gained
NM_001382347.1 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 6.21
Genes affected
MYO5A (HGNC:7602): (myosin VA) This gene is one of three myosin V heavy-chain genes, belonging to the myosin gene superfamily. Myosin V is a class of actin-based motor proteins involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment and mRNA translocation. The protein encoded by this gene is abundant in melanocytes and nerve cells. Mutations in this gene cause Griscelli syndrome type-1 (GS1) and neuroectodermal melanolysosomal disease, or Elejalde disease. [provided by RefSeq, Sep 2023]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-52376435-G-A is Pathogenic according to our data. Variant chr15-52376435-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 14069.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO5A | NM_001382347.1 | c.2332C>T | p.Arg778Ter | stop_gained | 19/42 | ENST00000399233.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO5A | ENST00000399233.7 | c.2332C>T | p.Arg778Ter | stop_gained | 19/42 | 5 | NM_001382347.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249330Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135282
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461840Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727216
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74448
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Griscelli syndrome type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A;A
Vest4
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at