dbSNP rs2290332: MYO5A:p.Asp1680Asp (chr15-52319254-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382347.1(MYO5A):c.5040T>C(p.Asp1680Asp) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.49

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1 link	c.5040T>C	p.Asp1680Asp	synonymous_variant	Exon 39 of 42	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7 link	c.5040T>C	p.Asp1680Asp	synonymous_variant	Exon 39 of 42	5	NM_001382347.1	ENSP00000382179.4		Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

30963

AN:

151924

Hom.:

3977

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.177

AC XY:

128617

AN XY:

727228

show subpopulations

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.:

AF XY:

0.206

AC XY:

15310

AN XY:

74338

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over