15-52317150-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_001382347.1(MYO5A):​c.5307G>A​(p.Leu1769Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,066 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

MYO5A
NM_001382347.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02
Variant links:
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 -7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 15-52317150-C-T is Benign according to our data. Variant chr15-52317150-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3609503.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.02 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000294 (43/1461806) while in subpopulation AFR AF= 0.000448 (15/33480). AF 95% confidence interval is 0.000276. There are 1 homozygotes in gnomad4_exome. There are 20 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO5ANM_001382347.1 linkc.5307G>A p.Leu1769Leu synonymous_variant Exon 40 of 42 ENST00000399233.7 NP_001369276.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO5AENST00000399233.7 linkc.5307G>A p.Leu1769Leu synonymous_variant Exon 40 of 42 5 NM_001382347.1 ENSP00000382179.4 Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461806
Hom.:
1
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152260
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
5.3
DANN
Benign
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs113484481; hg19: chr15-52609347; API