Variant chr15-52319048-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001382347.1(MYO5A):c.5234+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,613,874 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 9 hom. )

Consequence

MYO5A
NM_001382347.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.795

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-52319048-G-A is Benign according to our data. Variant chr15-52319048-G-A is described in ClinVar as [Benign]. Clinvar id is 1299850.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-52319048-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00178 (271/152358) while in subpopulation NFE AF= 0.00269 (183/68026). AF 95% confidence interval is 0.00237. There are 0 homozygotes in gnomad4. There are 122 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5A	NM_001382347.1 linkuse as main transcript	c.5234+12C>T		intron_variant		ENST00000399233.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5A	ENST00000399233.7 linkuse as main transcript	c.5234+12C>T		intron_variant		5	NM_001382347.1		Q9Y4I1-3

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

271

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00269

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00213

AC:

529

AN:

248742

Hom.:

AF XY:

0.00218

AC XY:

295

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.000645

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.00244

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00217

AC:

3172

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1520

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.00262

GnomAD4 genome

AF:

0.00178

AC:

271

AN:

152358

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00269

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00200

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 09, 2024	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.3

DANN

Benign

0.48

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