rs57599264

Positions:

• chr15-52364535-AC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001382347.1(MYO5A):​c.3309+18del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,591,530 control chromosomes in the GnomAD database, including 1,806 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (1703 hom., cov: 31)
  • Exomes 𝑓: 0.010 (103 hom.)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.23

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 -16 ACMG points.

• BP6: Variant 15-52364535-AC-A is Benign according to our data. Variant chr15-52364535-AC-A is described in ClinVar as [Benign]. Clinvar id is 255646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.3309+18del		intron_variant		ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.3309+18del		intron_variant		5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 12991 AN: 151214 Hom.: 1693 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.0567

GnomAD4 exome AF: 0.0101 AC: 14585 AN: 1440208 Hom.: 103 Cov.: 32 AF XY: 0.0104 AC XY: 7408 AN XY: 715174

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.00929

Gnomad4 ASJ exome AF: 0.00221

Gnomad4 EAS exome AF: 0.0167

Gnomad4 SAS exome AF: 0.0424

Gnomad4 FIN exome AF: 0.000492

Gnomad4 NFE exome AF: 0.00201

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0861 AC: 13035 AN: 151322 Hom.: 1703 Cov.: 31 AF XY: 0.0838 AC XY: 6202 AN XY: 73988

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0208

Gnomad4 SAS AF: 0.0575

Gnomad4 FIN AF: 0.000567

Gnomad4 NFE AF: 0.00334

Gnomad4 OTH AF: 0.0590

Alfa AF: 0.000609 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs57599264; hg19: chr15-52656732;