NM_001382347.1:c.4239+402C>T

Variant names:

• chr15-52339794-G-A
• rs752864
• NM_001382347.1:c.4239+402C>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.4239+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,042 control chromosomes in the GnomAD database, including 23,062 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 0.54 (23062 hom., cov: 31)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• 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 (NFE) allele frequency at 95% confidence interval = 0.6 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.4239+402C>T		intron	N/A	NP_001369276.1	Q9Y4I1-3
	MYO5A	NM_001382348.1		c.4311+402C>T		intron	N/A	NP_001369277.1
	MYO5A	NM_001382349.1		c.4311+402C>T		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.4239+402C>T		intron	N/A	ENSP00000382179.4	Q9Y4I1-3
	MYO5A	ENST00000399231.8	TSL:1	c.4239+402C>T		intron	N/A	ENSP00000382177.3	Q9Y4I1-1
	MYO5A	ENST00000356338.11	TSL:1	c.4158+402C>T		intron	N/A	ENSP00000348693.7	A0A8J8YWI7

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81675 AN: 151924 Hom.: 23051 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.537 AC: 81714 AN: 152042 Hom.: 23062 Cov.: 31 AF XY: 0.542 AC XY: 40248 AN XY: 74326

African (AFR) AF: 0.427 AC: 17671 AN: 41424

American (AMR) AF: 0.551 AC: 8427 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1795 AN: 3466

East Asian (EAS) AF: 0.156 AC: 808 AN: 5176

South Asian (SAS) AF: 0.389 AC: 1874 AN: 4820

European-Finnish (FIN) AF: 0.766 AC: 8110 AN: 10590

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

European-Non Finnish (NFE) AF: 0.605 AC: 41123 AN: 67964

Other (OTH) AF: 0.541 AC: 1143 AN: 2112

Alfa AF: 0.583 Hom.: 5269

Bravo AF: 0.517

Asia WGS AF: 0.275 AC: 961 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	2.3
DANN	Benign	0.52
PhyloP100		0.15
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: rs752864; hg19: chr15-52631991;