rs2222656

Positions:

• chr15-52480826-A-G

Variant summary

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

The NM_001382347.1(MYO5A):​c.28-47541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,222 control chromosomes in the GnomAD database, including 751 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 0.058 (751 hom., cov: 32)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.28-47541T>C		intron_variant		ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.28-47541T>C		intron_variant		5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8772 AN: 152106 Hom.: 745 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0213

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00304

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0579 AC: 8812 AN: 152222 Hom.: 751 Cov.: 32 AF XY: 0.0573 AC XY: 4267 AN XY: 74430

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00304

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0366 Hom.: 69

Bravo AF: 0.0638

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.21
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: rs2222656; hg19: chr15-52773023;