Variant rs201655854 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000169.3(GLA):c.640-854_640-853del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 111,616 control chromosomes in the GnomAD database, including 9 homozygotes. There are 383 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 9 hom., 383 hem., cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

GLA
NM_000169.3 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.567

Variant links:

Genes affected

GLA (HGNC:4296): (galactosidase alpha) This gene encodes a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. This enzyme predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose. A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry disease, a rare lysosomal storage disorder that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties. [provided by RefSeq, Jul 2008]

GLA links:

RPL36A-HNRNPH2 (HGNC:):

RPL36A-HNRNPH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-101399798-GCT-G is Benign according to our data. Variant chrX-101399798-GCT-G is described in ClinVar as [Benign]. Clinvar id is 42458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0118 (1312/111616) while in subpopulation SAS AF= 0.0424 (113/2666). AF 95% confidence interval is 0.036. There are 9 homozygotes in gnomad4. There are 383 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLA	NM_000169.3 linkuse as main transcript	c.640-854_640-853del		intron_variant		ENST00000218516.4
RPL36A-HNRNPH2	NM_001199973.2 linkuse as main transcript	c.300+4344_300+4345del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLA	ENST00000218516.4 linkuse as main transcript	c.640-854_640-853del		intron_variant		1	NM_000169.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1311

AN:

111560

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

382

AN XY:

33796

show subpopulations

Gnomad AFR

AF:

0.00264

Gnomad AMI

AF:

0.0102

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00189

Gnomad EAS

AF:

0.00448

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.00629

Gnomad MID

AF:

0.00855

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0207

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.0118

AC:

1312

AN:

111616

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

383

AN XY:

33862

show subpopulations

Gnomad4 AFR

AF:

0.00264

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.00189

Gnomad4 EAS

AF:

0.00449

Gnomad4 SAS

AF:

0.0424

Gnomad4 FIN

AF:

0.00629

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0205

Alfa

AF:

0.0155

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.0360

AC:

AN:

2522

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 20, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 14, 2010	- -

Fabry disease

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Oct 31, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jan 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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