chr15-52314142-G-A

Position:

chr15-52314142-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_001382347.1(MYO5A):c.5471C>T(p.Ser1824Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,609,896 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 2 hom. )

Consequence

MYO5A
NM_001382347.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 10.0

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 -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MYO5A. . Gene score misZ 3.0961 (greater than the threshold 3.09). Trascript score misZ 5.1368 (greater than threshold 3.09). GenCC has associacion of gene with Griscelli syndrome type 3, Griscelli syndrome type 1.

BP4

Computational evidence support a benign effect (MetaRNN=0.011045396).

BP6

Variant 15-52314142-G-A is Benign according to our data. Variant chr15-52314142-G-A is described in ClinVar as [Benign]. Clinvar id is 764740.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000338 (493/1457620) while in subpopulation SAS AF= 0.0000697 (6/86138). AF 95% confidence interval is 0.0000335. There are 2 homozygotes in gnomad4_exome. There are 235 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1 linkuse as main transcript	c.5471C>T	p.Ser1824Leu	missense_variant	41/42	ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7 linkuse as main transcript	c.5471C>T	p.Ser1824Leu	missense_variant	41/42	5	NM_001382347.1		Q9Y4I1-3

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000702

AC:

175

AN:

249254

Hom.:

AF XY:

0.000665

AC XY:

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00696

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000338

AC:

493

AN:

1457620

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

235

AN XY:

725372

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00781

Gnomad4 NFE exome

AF:

0.0000433

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000420

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00566

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000954

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.000464

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MYO5A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 02, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.;T;T;.;T;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.011

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.18

MutationAssessor

Uncertain

2.3

M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.8

D;D;.;.;.;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.021

D;D;.;.;.;D;D

Sift4G

Benign

0.092

T;T;T;T;T;T;T

Polyphen

0.11

B;B;.;.;.;.;.

Vest4

0.40

MVP

0.57

MPC

0.79

ClinPred

0.24

GERP RS

5.2

Varity_R

0.50

gMVP

0.61

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