chr15-52366175-G-A

Variant names:

• chr15-52366175-G-A
• rs10518684
• NM_001382347.1:c.3160+856C>T

Variant summary

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

The NM_001382347.1(MYO5A):​c.3160+856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 151,982 control chromosomes in the GnomAD database, including 261 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 0.050 (261 hom., cov: 31)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.3160+856C>T		intron_variant	Intron 23 of 41	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.3160+856C>T		intron_variant	Intron 23 of 41	5	NM_001382347.1	ENSP00000382179.4

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7603 AN: 151864 Hom.: 262 Cov.: 31

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0563

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

GnomAD4 genome AF: 0.0500 AC: 7595 AN: 151982 Hom.: 261 Cov.: 31 AF XY: 0.0528 AC XY: 3923 AN XY: 74282

African (AFR) AF: 0.0280 AC: 1162 AN: 41466

American (AMR) AF: 0.0571 AC: 872 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 123 AN: 3470

East Asian (EAS) AF: 0.192 AC: 993 AN: 5172

South Asian (SAS) AF: 0.0739 AC: 355 AN: 4806

European-Finnish (FIN) AF: 0.0671 AC: 706 AN: 10520

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3177 AN: 67978

Other (OTH) AF: 0.0557 AC: 117 AN: 2102

Alfa AF: 0.0456 Hom.: 338

Bravo AF: 0.0482

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.30
PhyloP100		-1.0
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: rs10518684; hg19: chr15-52658372;