rs10083673

Positions:

• chr15-52418143-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382347.1(MYO5A):​c.456-1842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,984 control chromosomes in the GnomAD database, including 21,041 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 0.48 (21041 hom., cov: 31)
• Consequence: MYO5A NM_001382347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.456-1842C>T		intron_variant		ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.456-1842C>T		intron_variant		5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73480 AN: 151870 Hom.: 21040 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.483 AC: 73482 AN: 151984 Hom.: 21041 Cov.: 31 AF XY: 0.488 AC XY: 36255 AN XY: 74276

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.509

Alfa AF: 0.591 Hom.: 53709

Bravo AF: 0.455

Asia WGS AF: 0.214 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs10083673; hg19: chr15-52710340;