15-52415803-G-C

Variant summary

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

The NM_001382347.1(MYO5A):c.612+342C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,968 control chromosomes in the GnomAD database, including 9,952 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 0.32 (9952 hom., cov: 31)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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 (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.612+342C>G		intron_variant		ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.612+342C>G		intron_variant		5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48322 AN: 151850 Hom.: 9920 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.319 AC: 48420 AN: 151968 Hom.: 9952 Cov.: 31 AF XY: 0.318 AC XY: 23661 AN XY: 74290

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.278

Alfa AF: 0.101 Hom.: 135

Bravo AF: 0.336

Asia WGS AF: 0.622 AC: 2162 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	7.6
Dann	Benign	0.74

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: rs1724630; hg19: chr15-52708000;