rs190656197

chr15-52372127-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001382347.1(MYO5A):c.2814G>A(p.Glu938=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,613,618 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (26 hom.)
• Consequence: MYO5A NM_001382347.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.329

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=-0.32).
• BP6: Variant 15-52372127-C-T is Benign according to our data. Variant chr15-52372127-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52372127-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.329 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0038 (579/152312) while in subpopulation NFE AF= 0.00656 (446/68028). AF 95% confidence interval is 0.00605. There are 3 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1	c.2814G>A	p.Glu938=	synonymous_variant	21/42	ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7	c.2814G>A	p.Glu938=	synonymous_variant	21/42	5	NM_001382347.1

Frequencies

GnomAD3 genomes AF: 0.00380 AC: 579 AN: 152194 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00656

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00339 AC: 845 AN: 249006 Hom.: 2 AF XY: 0.00345 AC XY: 466 AN XY: 135124

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.00235

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.00561

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00553 AC: 8084 AN: 1461306 Hom.: 26 Cov.: 31 AF XY: 0.00544 AC XY: 3956 AN XY: 726942

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00208

Gnomad4 FIN exome AF: 0.00172

Gnomad4 NFE exome AF: 0.00671

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.00380 AC: 579 AN: 152312 Hom.: 3 Cov.: 32 AF XY: 0.00383 AC XY: 285 AN XY: 74472

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00656

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00485 Hom.: 2

Bravo AF: 0.00355

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 25, 2015	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	MYO5A: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	6.3
Dann	Benign	0.51

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: rs190656197; hg19: chr15-52664324;