rs61363656

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.456-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,613,504 control chromosomes in the GnomAD database, including 2,705 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 272 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2433 hom. )

Consequence

MYO5A
NM_001382347.1 splice_region, intron

Scores

Splicing: ADA: 0.0002633

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.652

Publications

6 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 (BayesDel_noAF=-0.74).

BP6

Variant 15-52416305-T-C is Benign according to our data. Variant chr15-52416305-T-C is described in ClinVar as Benign. ClinVar VariationId is 255654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5A	NM_001382347.1 link	c.456-4A>G		splice_region_variant, intron_variant	Intron 4 of 41	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7 link	c.456-4A>G		splice_region_variant, intron_variant	Intron 4 of 41	5	NM_001382347.1	ENSP00000382179.4		Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes

AF:

0.0509

AC:

7741

AN:

152090

Hom.:

273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0609

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.0735

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0570

GnomAD2 exomes

AF:

0.0614

AC:

15233

AN:

248056

AF XY:

0.0601

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.0577

Gnomad ASJ exome

AF:

0.0408

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.0645

Gnomad NFE exome

AF:

0.0476

Gnomad OTH exome

AF:

0.0630

GnomAD4 exome

AF:

0.0526

AC:

76911

AN:

1461296

Hom.:

2433

Cov.:

AF XY:

0.0530

AC XY:

38506

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.0264

AC:

883

AN:

33456

American (AMR)

AF:

0.0566

AC:

2531

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

1015

AN:

26126

East Asian (EAS)

AF:

0.166

AC:

6573

AN:

39680

South Asian (SAS)

AF:

0.0749

AC:

6454

AN:

86224

European-Finnish (FIN)

AF:

0.0647

AC:

3451

AN:

53358

Middle Eastern (MID)

AF:

0.0635

AC:

366

AN:

5760

European-Non Finnish (NFE)

AF:

0.0469

AC:

52089

AN:

1111632

Other (OTH)

AF:

0.0588

AC:

3549

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

3568

7136

10705

14273

17841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2044

4088

6132

8176

10220

<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:

0.0508

AC:

7735

AN:

152208

Hom.:

272

Cov.:

AF XY:

0.0534

AC XY:

3974

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0284

AC:

1179

AN:

41532

American (AMR)

AF:

0.0608

AC:

930

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3468

East Asian (EAS)

AF:

0.182

AC:

939

AN:

5172

South Asian (SAS)

AF:

0.0728

AC:

351

AN:

4824

European-Finnish (FIN)

AF:

0.0660

AC:

699

AN:

10598

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0478

AC:

3251

AN:

68008

Other (OTH)

AF:

0.0569

AC:

120

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

370

740

1109

1479

1849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0472

Hom.:

Bravo

AF:

0.0490

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.0463

EpiControl

AF:

0.0456

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 28, 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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.6

(source)

DANN

Benign

0.66

PhyloP100

-0.65

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.14

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