NM_001382347.1:c.1880T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382347.1(MYO5A):c.1880T>C(p.Met627Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,614,044 control chromosomes in the GnomAD database, including 1,457 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.053 ( 620 hom., cov: 32)

Exomes 𝑓: 0.011 ( 837 hom. )

Consequence

MYO5A
NM_001382347.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.890

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010196269).

BP6

Variant 15-52384195-A-G is Benign according to our data. Variant chr15-52384195-A-G is described in ClinVar as [Benign]. Clinvar id is 255640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52384195-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1 link	c.1880T>C	p.Met627Thr	missense_variant	Exon 15 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.1880T>C	p.Met627Thr	missense_variant	Exon 15 of 42	5	NM_001382347.1	ENSP00000382179.4		Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes

AF:

0.0529

AC:

8038

AN:

152072

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.0587

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.0336

GnomAD3 exomes

AF:

0.0232

AC:

5794

AN:

249480

Hom.:

334

AF XY:

0.0231

AC XY:

3128

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.00802

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0178

Gnomad SAS exome

AF:

0.0641

Gnomad FIN exome

AF:

0.000649

Gnomad NFE exome

AF:

0.00352

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0113

AC:

16456

AN:

1461854

Hom.:

837

Cov.:

AF XY:

0.0122

AC XY:

8895

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.00865

Gnomad4 ASJ exome

AF:

0.00275

Gnomad4 EAS exome

AF:

0.0215

Gnomad4 SAS exome

AF:

0.0601

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.00250

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0529

AC:

8058

AN:

152190

Hom.:

620

Cov.:

AF XY:

0.0517

AC XY:

3851

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.0144

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.0209

Gnomad4 SAS

AF:

0.0581

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00306

Gnomad4 OTH

AF:

0.0370

Alfa

AF:

0.0133

Hom.:

265

Bravo

AF:

0.0591

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.161

AC:

657

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.0276

AC:

3334

Asia WGS

AF:

0.0610

AC:

215

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00320

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

- -

Jun 09, 2021

GeneDx

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

- -

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

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.5

DANN

Benign

0.29

DEOGEN2

Benign

0.19

T;.;T;T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.70

T;T;T;T;T;T

MetaRNN

Benign

0.0010

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.1

N;N;.;.;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.18

N;N;.;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.82

T;T;.;T;T;T

Sift4G

Benign

0.87

T;T;T;T;T;T

Polyphen

0.0

B;B;.;.;.;.

Vest4

0.011

MPC

0.43

ClinPred

0.0041

GERP RS

-2.2

Varity_R

0.029

gMVP

0.14

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

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