NM_001382347.1:c.612+342C>G

Variant names:

• chr15-52415803-G-C
• rs1724630
• NM_001382347.1:c.612+342C>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.612+342C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,968 control chromosomes in the GnomAD database, including 9,952 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 0.32 (9952 hom., cov: 31)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	NM_001382347.1	MANE Select	c.612+342C>G		intron	N/A	NP_001369276.1
	MYO5A	NM_001382348.1		c.684+342C>G		intron	N/A	NP_001369277.1
	MYO5A	NM_001382349.1		c.684+342C>G		intron	N/A	NP_001369278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.612+342C>G		intron	N/A	ENSP00000382179.4
	MYO5A	ENST00000399231.8	TSL:1	c.612+342C>G		intron	N/A	ENSP00000382177.3
	MYO5A	ENST00000356338.11	TSL:1	c.612+342C>G		intron	N/A	ENSP00000348693.7

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48322 AN: 151850 Hom.: 9920 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.319 AC: 48420 AN: 151968 Hom.: 9952 Cov.: 31 AF XY: 0.318 AC XY: 23661 AN XY: 74290

African (AFR) AF: 0.531 AC: 21968 AN: 41406

American (AMR) AF: 0.281 AC: 4291 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3466

East Asian (EAS) AF: 0.664 AC: 3439 AN: 5176

South Asian (SAS) AF: 0.510 AC: 2459 AN: 4822

European-Finnish (FIN) AF: 0.100 AC: 1059 AN: 10570

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13543 AN: 67950

Other (OTH) AF: 0.278 AC: 587 AN: 2112

Alfa AF: 0.101 Hom.: 135

Bravo AF: 0.336

Asia WGS AF: 0.622 AC: 2162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.74
PhyloP100		0.028
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: rs1724630; hg19: chr15-52708000;