rs16964944

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

Griscelli syndrome type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Griscelli syndrome type 3
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 255640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.0232

AC:

5794

AN:

249480

AF XY:

0.0231

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 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

African (AFR)

AF:

0.178

AC:

5959

AN:

33478

American (AMR)

AF:

0.00865

AC:

387

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00275

AC:

AN:

26136

East Asian (EAS)

AF:

0.0215

AC:

852

AN:

39694

South Asian (SAS)

AF:

0.0601

AC:

5183

AN:

86258

European-Finnish (FIN)

AF:

0.000655

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0163

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00250

AC:

2777

AN:

1111984

Other (OTH)

AF:

0.0182

AC:

1097

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

974

1948

2921

3895

4869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0529

AC:

8058

AN:

152190

Hom.:

620

Cov.:

AF XY:

0.0517

AC XY:

3851

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.172

AC:

7146

AN:

41492

American (AMR)

AF:

0.0144

AC:

221

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

3460

East Asian (EAS)

AF:

0.0209

AC:

108

AN:

5170

South Asian (SAS)

AF:

0.0581

AC:

280

AN:

4818

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00306

AC:

208

AN:

68022

Other (OTH)

AF:

0.0370

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

344

687

1031

1374

1718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0222

Hom.:

698

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

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

(source)

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;.;.;.;.

PhyloP100

0.89

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over