chr15-52433803-C-T

Variant names:

• chr15-52433803-C-T
• rs7176061
• NM_001382347.1:c.28-518G>A

Variant summary

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

The NM_001382347.1(MYO5A):​c.28-518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,730 control chromosomes in the GnomAD database, including 22,933 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 0.53 (22933 hom., cov: 30)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 2 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: G2P, ClinGen, 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382347.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	NM_001382347.1	MANE Select	c.28-518G>A		intron	N/A	NP_001369276.1	Q9Y4I1-3
	MYO5A	NM_001382348.1		c.100-518G>A		intron	N/A	NP_001369277.1
	MYO5A	NM_001382349.1		c.100-518G>A		intron	N/A	NP_001369278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.28-518G>A		intron	N/A	ENSP00000382179.4	Q9Y4I1-3
	MYO5A	ENST00000399231.8	TSL:1	c.28-518G>A		intron	N/A	ENSP00000382177.3	Q9Y4I1-1
	MYO5A	ENST00000356338.11	TSL:1	c.28-518G>A		intron	N/A	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80989 AN: 151614 Hom.: 22892 Cov.: 30

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.534 AC: 81085 AN: 151730 Hom.: 22933 Cov.: 30 AF XY: 0.531 AC XY: 39378 AN XY: 74172

African (AFR) AF: 0.658 AC: 27204 AN: 41362

American (AMR) AF: 0.533 AC: 8138 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1925 AN: 3464

East Asian (EAS) AF: 0.850 AC: 4402 AN: 5176

South Asian (SAS) AF: 0.694 AC: 3337 AN: 4806

European-Finnish (FIN) AF: 0.308 AC: 3233 AN: 10488

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31238 AN: 67876

Other (OTH) AF: 0.538 AC: 1129 AN: 2100

Alfa AF: 0.486 Hom.: 6395

Bravo AF: 0.554

Asia WGS AF: 0.790 AC: 2744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.73
DANN	Benign	0.44
PhyloP100		-0.72
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: rs7176061; hg19: chr15-52726000;