rs1724593

Variant names:

• chr15-52444547-A-C
• rs1724593
• NM_001382347.1:c.28-11262T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382347.1(MYO5A):​c.28-11262T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,134 control chromosomes in the GnomAD database, including 5,401 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 0.22 (5401 hom., cov: 32)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 7 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

ENSG00000298318 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.28-11262T>G		intron_variant	Intron 1 of 41	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.28-11262T>G		intron_variant	Intron 1 of 41	5	NM_001382347.1	ENSP00000382179.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33990 AN: 152016 Hom.: 5382 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.224 AC: 34057 AN: 152134 Hom.: 5401 Cov.: 32 AF XY: 0.224 AC XY: 16691 AN XY: 74406

African (AFR) AF: 0.379 AC: 15713 AN: 41460

American (AMR) AF: 0.224 AC: 3431 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3466

East Asian (EAS) AF: 0.589 AC: 3043 AN: 5168

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4814

European-Finnish (FIN) AF: 0.0438 AC: 465 AN: 10614

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8621 AN: 68008

Other (OTH) AF: 0.193 AC: 407 AN: 2110

Alfa AF: 0.159 Hom.: 1233

Bravo AF: 0.243

Asia WGS AF: 0.466 AC: 1618 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.75
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1724593; hg19: chr15-52736744;