rs11637651

chr15-52372211-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001382347.1(MYO5A):c.2730C>T(p.Ile910=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,613,460 control chromosomes in the GnomAD database, including 3,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (238 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3545 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.643

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 15-52372211-G-A is Benign according to our data. Variant chr15-52372211-G-A is described in ClinVar as [Benign]. Clinvar id is 255642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.643 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.2730C>T	p.Ile910=	synonymous_variant	21/42	ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.2730C>T	p.Ile910=	synonymous_variant	21/42	5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7829 AN: 152106 Hom.: 237 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0517

GnomAD3 exomes AF: 0.0578 AC: 14393 AN: 248954 Hom.: 491 AF XY: 0.0615 AC XY: 8306 AN XY: 135042

Gnomad AFR exome AF: 0.0310

Gnomad AMR exome AF: 0.0269

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.0714

Gnomad SAS exome AF: 0.0968

Gnomad FIN exome AF: 0.0260

Gnomad NFE exome AF: 0.0669

Gnomad OTH exome AF: 0.0575

GnomAD4 exome AF: 0.0666 AC: 97256 AN: 1461236 Hom.: 3545 Cov.: 32 AF XY: 0.0677 AC XY: 49182 AN XY: 726940

Gnomad4 AFR exome AF: 0.0291

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0281

Gnomad4 EAS exome AF: 0.0670

Gnomad4 SAS exome AF: 0.0943

Gnomad4 FIN exome AF: 0.0275

Gnomad4 NFE exome AF: 0.0699

Gnomad4 OTH exome AF: 0.0645

GnomAD4 genome AF: 0.0515 AC: 7840 AN: 152224 Hom.: 238 Cov.: 32 AF XY: 0.0494 AC XY: 3675 AN XY: 74440

Gnomad4 AFR AF: 0.0305

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.0920

Gnomad4 FIN AF: 0.0205

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0569 Hom.: 125

Bravo AF: 0.0502

Asia WGS AF: 0.0670 AC: 233 AN: 3478

EpiCase AF: 0.0661

EpiControl AF: 0.0669

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	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

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	-0.36
Cadd	Benign	1.7
Dann	Benign	0.81

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: rs11637651; hg19: chr15-52664408; COSMIC: COSV62558141;