rs752864

Positions:

• chr15-52339794-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382347.1(MYO5A):​c.4239+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,042 control chromosomes in the GnomAD database, including 23,062 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23062 hom., cov: 31)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.4239+402C>T		intron_variant		ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.4239+402C>T		intron_variant		5	NM_001382347.1	ENSP00000382179

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81675 AN: 151924 Hom.: 23051 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81714 AN: 152042 Hom.: 23062 Cov.: 31 AF XY: 0.542 AC XY: 40248 AN XY: 74326

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.541

Alfa AF: 0.583 Hom.: 5269

Bravo AF: 0.517

Asia WGS AF: 0.275 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs752864; hg19: chr15-52631991;