Variant 15-52389376-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382347.1(MYO5A):c.1543-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,602,854 control chromosomes in the GnomAD database, including 774,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 64826 hom., cov: 30)

Exomes 𝑓: 0.99 ( 709307 hom. )

Consequence

MYO5A
NM_001382347.1 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.62

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-52389376-A-G is Benign according to our data. Variant chr15-52389376-A-G is described in ClinVar as [Benign]. Clinvar id is 255639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-52389376-A-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
MYO5A	NM_001382347.1 linkuse as main transcript	c.1543-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7 linkuse as main transcript	c.1543-13T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001382347.1		Q9Y4I1-3

Frequencies

GnomAD3 genomes

AF:

0.933

AC:

139141

AN:

149212

Hom.:

64799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.976

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.944

GnomAD3 exomes

AF:

0.969

AC:

240664

AN:

248428

Hom.:

117205

AF XY:

0.971

AC XY:

130788

AN XY:

134704

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.987

Gnomad ASJ exome

AF:

0.998

Gnomad EAS exome

AF:

0.982

Gnomad SAS exome

AF:

0.936

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.996

Gnomad OTH exome

AF:

0.985

GnomAD4 exome

AF:

0.988

AC:

1435844

AN:

1453544

Hom.:

709307

Cov.:

AF XY:

0.987

AC XY:

714208

AN XY:

723470

show subpopulations

Gnomad4 AFR exome

AF:

0.770

Gnomad4 AMR exome

AF:

0.986

Gnomad4 ASJ exome

AF:

0.997

Gnomad4 EAS exome

AF:

0.979

Gnomad4 SAS exome

AF:

0.945

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.997

Gnomad4 OTH exome

AF:

0.977

GnomAD4 genome

AF:

0.932

AC:

139215

AN:

149310

Hom.:

64826

Cov.:

AF XY:

0.934

AC XY:

68268

AN XY:

73068

show subpopulations

Gnomad4 AFR

AF:

0.768

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.999

Gnomad4 EAS

AF:

0.979

Gnomad4 SAS

AF:

0.944

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.943

Alfa

AF:

0.966

Hom.:

13212

Bravo

AF:

0.904

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Griscelli syndrome type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.045

DANN

Benign

0.62

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