chr15-52319154-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_001382347.1(MYO5A):c.5140G>A(p.Val1714Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00406 in 1,614,196 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 22 hom. )
Consequence
MYO5A
NM_001382347.1 missense
NM_001382347.1 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 6.17
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 Benign. Variant got -12 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MYO5A
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010131419).
BP6
?
Variant 15-52319154-C-T is Benign according to our data. Variant chr15-52319154-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 235746.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00259 (394/152308) while in subpopulation NFE AF= 0.00415 (282/68016). AF 95% confidence interval is 0.00375. There are 0 homozygotes in gnomad4. There are 178 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO5A | NM_001382347.1 | c.5140G>A | p.Val1714Ile | missense_variant | 39/42 | ENST00000399233.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO5A | ENST00000399233.7 | c.5140G>A | p.Val1714Ile | missense_variant | 39/42 | 5 | NM_001382347.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00259 AC: 394AN: 152190Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00239 AC: 596AN: 249618Hom.: 3 AF XY: 0.00229 AC XY: 310AN XY: 135408
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GnomAD4 exome AF: 0.00421 AC: 6152AN: 1461888Hom.: 22 Cov.: 32 AF XY: 0.00406 AC XY: 2953AN XY: 727246
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GnomAD4 genome ? AF: 0.00259 AC: 394AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.00239 AC XY: 178AN XY: 74468
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ESP6500AA
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34
ExAC
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268
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3478
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | MYO5A: PP2, BS1, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 29, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;.;N;N
REVEL
Benign
Sift
Benign
T;T;.;.;.;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;P;.;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at