rs57599264

Variant names:

• chr15-52364535-AC-A
• rs57599264
• NM_001382347.1:c.3309+18delG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001382347.1(MYO5A):​c.3309+18delG 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
• Publications: 1 publications found

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]

MYO5A Gene-Disease associations (from GenCC):

• Griscelli syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Griscelli syndrome type 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.3309+18delG		intron_variant	Intron 24 of 41	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.3309+18delG		intron_variant	Intron 24 of 41	5	NM_001382347.1	ENSP00000382179.4

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

GnomAD2 exomes AF: 0.0203 AC: 4686 AN: 230450 AF XY: 0.0180

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.00817

Gnomad ASJ exome AF: 0.00188

Gnomad EAS exome AF: 0.0125

Gnomad FIN exome AF: 0.000378

Gnomad NFE exome AF: 0.00240

Gnomad OTH exome AF: 0.0107

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.228 AC: 6601 AN: 28926

American (AMR) AF: 0.00929 AC: 393 AN: 42300

Ashkenazi Jewish (ASJ) AF: 0.00221 AC: 57 AN: 25790

East Asian (EAS) AF: 0.0167 AC: 657 AN: 39266

South Asian (SAS) AF: 0.0424 AC: 3358 AN: 79112

European-Finnish (FIN) AF: 0.000492 AC: 26 AN: 52824

Middle Eastern (MID) AF: 0.0189 AC: 107 AN: 5654

European-Non Finnish (NFE) AF: 0.00201 AC: 2229 AN: 1107050

Other (OTH) AF: 0.0195 AC: 1157 AN: 59286

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.291 AC: 11883 AN: 40766

American (AMR) AF: 0.0260 AC: 396 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5180

South Asian (SAS) AF: 0.0575 AC: 276 AN: 4796

European-Finnish (FIN) AF: 0.000567 AC: 6 AN: 10588

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00334 AC: 227 AN: 67968

Other (OTH) AF: 0.0590 AC: 124 AN: 2102

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

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs57599264; hg19: chr15-52656732;