15-52397434-T-G

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.1086A>C(p.Glu362Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,613,964 control chromosomes in the GnomAD database, including 776,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64899 hom., cov: 31)

Exomes 𝑓: 0.99 ( 711837 hom. )

Consequence

MYO5A
NM_001382347.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.136

Publications

29 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=1.2907003E-6).

BP6

Variant 15-52397434-T-G is Benign according to our data. Variant chr15-52397434-T-G is described in ClinVar as [Benign]. Clinvar id is 1321831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1 link	c.1086A>C	p.Glu362Asp	missense_variant	Exon 10 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.1086A>C	p.Glu362Asp	missense_variant	Exon 10 of 42	5	NM_001382347.1	ENSP00000382179.4		Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes

AF:

0.916

AC:

139254

AN:

152086

Hom.:

64873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.718

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.975

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.942

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.939

GnomAD2 exomes

AF:

0.969

AC:

241352

AN:

249110

AF XY:

0.971

show subpopulations

Gnomad AFR exome

AF:

0.709

Gnomad AMR exome

AF:

0.987

Gnomad ASJ exome

AF:

0.998

Gnomad EAS exome

AF:

0.982

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.996

Gnomad OTH exome

AF:

0.985

GnomAD4 exome

AF:

0.986

AC:

1440945

AN:

1461760

Hom.:

711837

Cov.:

AF XY:

0.985

AC XY:

716463

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.714

AC:

23884

AN:

33474

American (AMR)

AF:

0.986

AC:

44099

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

26064

AN:

26136

East Asian (EAS)

AF:

0.979

AC:

38837

AN:

39688

South Asian (SAS)

AF:

0.940

AC:

81061

AN:

86250

European-Finnish (FIN)

AF:

0.999

AC:

53385

AN:

53420

Middle Eastern (MID)

AF:

0.981

AC:

5658

AN:

5766

European-Non Finnish (NFE)

AF:

0.997

AC:

1109094

AN:

1111910

Other (OTH)

AF:

0.975

AC:

58863

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1053

2105

3158

4210

5263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21640

43280

64920

86560

108200

<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:

0.915

AC:

139327

AN:

152204

Hom.:

64899

Cov.:

AF XY:

0.918

AC XY:

68324

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.717

AC:

29756

AN:

41474

American (AMR)

AF:

0.975

AC:

14905

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

3467

AN:

3472

East Asian (EAS)

AF:

0.979

AC:

5075

AN:

5184

South Asian (SAS)

AF:

0.943

AC:

4543

AN:

4820

European-Finnish (FIN)

AF:

0.999

AC:

10610

AN:

10616

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.997

AC:

67798

AN:

68030

Other (OTH)

AF:

0.936

AC:

1974

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

474

948

1422

1896

2370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.966

Hom.:

200764

Bravo

AF:

0.905

TwinsUK

AF:

0.997

AC:

3696

ALSPAC

AF:

0.996

AC:

3838

ESP6500AA

AF:

0.729

AC:

2881

ESP6500EA

AF:

0.996

AC:

8301

ExAC

AF:

0.963

AC:

116326

Asia WGS

AF:

0.932

AC:

3237

AN:

3476

EpiCase

AF:

0.996

EpiControl

AF:

0.997

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Griscelli syndrome type 1

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

0.059

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.2

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.23

T;.;T;T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.21

T;T;T;T;T;T

MetaRNN

Benign

0.0000013

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.82

L;L;.;.;.;.

PhyloP100

0.14

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.010

N;N;.;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.70

T;T;.;T;T;T

Sift4G

Benign

0.96

T;T;T;T;T;T

Polyphen

0.0

B;B;.;.;.;.

Vest4

0.099

MutPred

0.47

Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);

MPC

0.34

ClinPred

0.00070

GERP RS

-4.7

Varity_R

0.069

gMVP

0.16

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