Genetic Variant MYO5A:p.Ser1138Ser (chr15-52359977-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382347.1(MYO5A):c.3414A>G(p.Ser1138Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,605,090 control chromosomes in the GnomAD database, including 4,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 2246 hom., cov: 32)

Exomes 𝑓: 0.017 ( 2428 hom. )

Consequence

MYO5A
NM_001382347.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 15-52359977-T-C is Benign according to our data. Variant chr15-52359977-T-C is described in ClinVar as Benign. ClinVar VariationId is 255647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382347.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYO5A	NM_001382347.1	MANE Select	c.3414A>G	p.Ser1138Ser	synonymous	Exon 25 of 42	NP_001369276.1
MYO5A	NM_001382348.1		c.3486A>G	p.Ser1162Ser	synonymous	Exon 26 of 43	NP_001369277.1
MYO5A	NM_001382349.1		c.3486A>G	p.Ser1162Ser	synonymous	Exon 26 of 42	NP_001369278.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYO5A	ENST00000399233.7	TSL:5 MANE Select	c.3414A>G	p.Ser1138Ser	synonymous	Exon 25 of 42	ENSP00000382179.4
MYO5A	ENST00000399231.8	TSL:1	c.3414A>G	p.Ser1138Ser	synonymous	Exon 25 of 41	ENSP00000382177.3
MYO5A	ENST00000356338.11	TSL:1	c.3414A>G	p.Ser1138Ser	synonymous	Exon 25 of 41	ENSP00000348693.7

Frequencies

GnomAD3 genomes

AF:

0.0969

AC:

14746

AN:

152138

Hom.:

2223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0292

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0289

Gnomad SAS

AF:

0.0622

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.0617

GnomAD2 exomes

AF:

0.0351

AC:

8712

AN:

247932

AF XY:

0.0322

show subpopulations

Gnomad AFR exome

AF:

0.337

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.00340

Gnomad EAS exome

AF:

0.0255

Gnomad FIN exome

AF:

0.000652

Gnomad NFE exome

AF:

0.00379

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0165

AC:

23997

AN:

1452834

Hom.:

2428

Cov.:

AF XY:

0.0168

AC XY:

12170

AN XY:

723206

show subpopulations

African (AFR)

AF:

0.347

AC:

11489

AN:

33154

American (AMR)

AF:

0.0153

AC:

684

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00342

AC:

AN:

26036

East Asian (EAS)

AF:

0.0338

AC:

1338

AN:

39620

South Asian (SAS)

AF:

0.0642

AC:

5508

AN:

85850

European-Finnish (FIN)

AF:

0.000657

AC:

AN:

53304

Middle Eastern (MID)

AF:

0.0249

AC:

143

AN:

5740

European-Non Finnish (NFE)

AF:

0.00260

AC:

2872

AN:

1104450

Other (OTH)

AF:

0.0306

AC:

1839

AN:

60074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

921

1841

2762

3682

4603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.0973

AC:

14817

AN:

152256

Hom.:

2246

Cov.:

AF XY:

0.0949

AC XY:

7062

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.326

AC:

13532

AN:

41504

American (AMR)

AF:

0.0291

AC:

446

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.0282

AC:

146

AN:

5186

South Asian (SAS)

AF:

0.0616

AC:

297

AN:

4822

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00340

AC:

231

AN:

68030

Other (OTH)

AF:

0.0682

AC:

144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

510

1020

1529

2039

2549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0408

Hom.:

2511

Bravo

AF:

0.110

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00351

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.6

(source)

DANN

Benign

0.42

PhyloP100

-1.2

PromoterAI

0.032

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over