15-52503597-C-T

Position:

• chr15-52503597-C-T

Variant summary

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

The NM_001382347.1(MYO5A):​c.27+25183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,676 control chromosomes in the GnomAD database, including 35,761 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 0.67 (35761 hom., cov: 33)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.27+25183G>A		intron_variant		ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.27+25183G>A		intron_variant		5	NM_001382347.1	ENSP00000382179

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101005 AN: 151558 Hom.: 35755 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.666 AC: 101016 AN: 151676 Hom.: 35761 Cov.: 33 AF XY: 0.673 AC XY: 49847 AN XY: 74092

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.676

Alfa AF: 0.718 Hom.: 4949

Bravo AF: 0.650

Asia WGS AF: 0.684 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.14

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: rs34602777; hg19: chr15-52795794;