rs1058219

Positions:

chr15-52351367-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001382347.1(MYO5A):c.3736C>T(p.Arg1246Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,614,020 control chromosomes in the GnomAD database, including 21,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 1810 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19806 hom. )

Consequence

MYO5A
NM_001382347.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.07

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:

MYO5A (HGNC:):

MYO5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 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=0.0016999841).

BP6

Variant 15-52351367-G-A is Benign according to our data. Variant chr15-52351367-G-A is described in ClinVar as [Benign]. Clinvar id is 255650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52351367-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5A	NM_001382347.1 linkuse as main transcript	c.3736C>T	p.Arg1246Cys	missense_variant	28/42	ENST00000399233.7	NP_001369276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5A	ENST00000399233.7 linkuse as main transcript	c.3736C>T	p.Arg1246Cys	missense_variant	28/42	5	NM_001382347.1	ENSP00000382179.4		Q9Y4I1-3F8WE88

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22847

AN:

152048

Hom.:

1816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.156

AC:

38829

AN:

249556

Hom.:

3180

AF XY:

0.156

AC XY:

21155

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.163

AC:

237836

AN:

1461854

Hom.:

19806

Cov.:

AF XY:

0.162

AC XY:

118133

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.150

AC:

22838

AN:

152166

Hom.:

1810

Cov.:

AF XY:

0.148

AC XY:

10988

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.168

Hom.:

3046

Bravo

AF:

0.153

TwinsUK

AF:

0.166

AC:

617

ALSPAC

AF:

0.169

AC:

650

ESP6500AA

AF:

0.102

AC:

414

ESP6500EA

AF:

0.168

AC:

1402

ExAC

AF:

0.154

AC:

18638

Asia WGS

AF:

0.145

AC:

506

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.179

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Griscelli syndrome type 1

Benign:2

Benign, no assertion criteria provided	literature only	OMIM	Jul 01, 1997	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.;T;T;.;T;T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.075

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

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

MetaRNN

Benign

0.0017

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.5

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

REVEL

Benign

0.10

Sift

Uncertain

0.0060

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

Sift4G

Uncertain

0.018

D;D;D;D;D;D;D;T;T

Polyphen

0.59

P;D;.;.;.;.;.;.;.

Vest4

0.16

MPC

0.77

ClinPred

0.033

GERP RS

2.3

Varity_R

0.14

gMVP

0.42

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