NM_001382347.1:c.27+7365A>G

Variant names:

• chr15-52521415-T-C
• rs1615028
• NM_001382347.1:c.27+7365A>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.27+7365A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,190 control chromosomes in the GnomAD database, including 1,321 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 0.12 (1321 hom., cov: 31)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854
• Publications: 3 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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1	c.27+7365A>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.27+7365A>G		intron_variant	Intron 1 of 41	5	NM_001382347.1	ENSP00000382179.4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18011 AN: 152072 Hom.: 1321 Cov.: 31

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.118 AC: 18025 AN: 152190 Hom.: 1321 Cov.: 31 AF XY: 0.117 AC XY: 8671 AN XY: 74396

African (AFR) AF: 0.0512 AC: 2128 AN: 41544

American (AMR) AF: 0.125 AC: 1909 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0985 AC: 342 AN: 3472

East Asian (EAS) AF: 0.0858 AC: 445 AN: 5184

South Asian (SAS) AF: 0.169 AC: 814 AN: 4824

European-Finnish (FIN) AF: 0.105 AC: 1107 AN: 10588

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10881 AN: 67982

Other (OTH) AF: 0.134 AC: 282 AN: 2108

Alfa AF: 0.140 Hom.: 540

Bravo AF: 0.115

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.85
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: rs1615028; hg19: chr15-52813612;