rs2290332

Positions:

• chr15-52319254-A-G
• chr15-52319254-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001382347.1(MYO5A):​c.5040T>C​(p.Asp1680=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,613,882 control chromosomes in the GnomAD database, including 32,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3977 hom., cov: 32)
  • Exomes 𝑓: 0.17 (28297 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.49

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-52319254-A-G is Benign according to our data. Variant chr15-52319254-A-G is described in ClinVar as [Benign]. Clinvar id is 255655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.5040T>C	p.Asp1680=	synonymous_variant	39/42	ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.5040T>C	p.Asp1680=	synonymous_variant	39/42	5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30963 AN: 151924 Hom.: 3977 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.178

GnomAD3 exomes AF: 0.227 AC: 56554 AN: 249560 Hom.: 8857 AF XY: 0.226 AC XY: 30567 AN XY: 135376

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.601

Gnomad SAS exome AF: 0.360

Gnomad FIN exome AF: 0.0705

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.172 AC: 251218 AN: 1461840 Hom.: 28297 Cov.: 34 AF XY: 0.177 AC XY: 128617 AN XY: 727228

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.0761

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.204 AC: 30982 AN: 152042 Hom.: 3977 Cov.: 32 AF XY: 0.206 AC XY: 15310 AN XY: 74338

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.0653

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.179

Alfa AF: 0.163 Hom.: 2869

Bravo AF: 0.216

Asia WGS AF: 0.497 AC: 1726 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.139

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 06, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.27
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2290332; hg19: chr15-52611451; COSMIC: COSV62558116; COSMIC: COSV62558116;