NM_001382347.1:c.1053+2821G>A

Variant names:

• chr15-52402466-C-T
• rs1632403
• NM_001382347.1:c.1053+2821G>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.1053+2821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 152,156 control chromosomes in the GnomAD database, including 249 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 0.053 (249 hom., cov: 32)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.1053+2821G>A		intron_variant	Intron 9 of 41	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7	c.1053+2821G>A		intron_variant	Intron 9 of 41	5	NM_001382347.1	ENSP00000382179.4

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7981 AN: 152038 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.0936

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0720

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0547

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

GnomAD4 genome AF: 0.0525 AC: 7992 AN: 152156 Hom.: 249 Cov.: 32 AF XY: 0.0503 AC XY: 3738 AN XY: 74382

African (AFR) AF: 0.0309 AC: 1284 AN: 41510

American (AMR) AF: 0.0394 AC: 603 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3468

East Asian (EAS) AF: 0.0728 AC: 376 AN: 5168

South Asian (SAS) AF: 0.0934 AC: 450 AN: 4818

European-Finnish (FIN) AF: 0.0205 AC: 217 AN: 10586

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0697 AC: 4742 AN: 68008

Other (OTH) AF: 0.0556 AC: 117 AN: 2106

Alfa AF: 0.0572 Hom.: 165

Bravo AF: 0.0512

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.9
DANN	Benign	0.68
PhyloP100		0.21
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: rs1632403; hg19: chr15-52694663;