rs2071226

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000169.3(GLA):c.194+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 1,188,364 control chromosomes in the GnomAD database, including 231 homozygotes. There are 1,864 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 28 hom., 190 hem., cov: 24)

Exomes 𝑓: 0.0048 ( 203 hom. 1674 hem. )

Consequence

GLA
NM_000169.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.0110

Publications

4 publications found

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:48349): (RPL36A-HNRNPH2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ribosomal protein L36a and heterogeneous nuclear ribonucleoprotein H2 (H') genes on chromosome X. The read-through transcript produces a protein with similarity to the protein encoded by the upstream locus, ribosomal protein L36a. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jan 2011]

RPL36A-HNRNPH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant X-101407693-T-C is Benign according to our data. Variant chrX-101407693-T-C is described in ClinVar as Benign. ClinVar VariationId is 193058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLA	NM_000169.3 link	c.194+17A>G		intron_variant	Intron 1 of 6	ENST00000218516.4	NP_000160.1	P06280Q53Y83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLA	ENST00000218516.4 link	c.194+17A>G		intron_variant	Intron 1 of 6	1	NM_000169.3	ENSP00000218516.4		P06280
RPL36A-HNRNPH2	ENST00000409170.3 link	c.301-4243T>C		intron_variant	Intron 4 of 4	4		ENSP00000386655.4		H7BZ11

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

566

AN:

110784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00391

Gnomad ASJ

AF:

0.000380

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.00531

Gnomad FIN

AF:

0.00645

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00470

GnomAD2 exomes

AF:

0.0109

AC:

1992

AN:

182637

AF XY:

0.0100

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.00581

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00475

AC:

5121

AN:

1077524

Hom.:

203

Cov.:

AF XY:

0.00485

AC XY:

1674

AN XY:

345174

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

25998

American (AMR)

AF:

0.000313

AC:

AN:

35194

Ashkenazi Jewish (ASJ)

AF:

0.000260

AC:

AN:

19254

East Asian (EAS)

AF:

0.131

AC:

3956

AN:

30111

South Asian (SAS)

AF:

0.00464

AC:

249

AN:

53670

European-Finnish (FIN)

AF:

0.00641

AC:

260

AN:

40531

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

4082

European-Non Finnish (NFE)

AF:

0.000267

AC:

220

AN:

823260

Other (OTH)

AF:

0.00903

AC:

410

AN:

45424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

205

410

616

821

1026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00512

AC:

567

AN:

110840

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

190

AN XY:

33216

show subpopulations

African (AFR)

AF:

0.000131

AC:

AN:

30442

American (AMR)

AF:

0.00391

AC:

AN:

10499

Ashkenazi Jewish (ASJ)

AF:

0.000380

AC:

AN:

2634

East Asian (EAS)

AF:

0.125

AC:

438

AN:

3505

South Asian (SAS)

AF:

0.00571

AC:

AN:

2627

European-Finnish (FIN)

AF:

0.00645

AC:

AN:

5894

Middle Eastern (MID)

AF:

0.00463

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000398

AC:

AN:

52830

Other (OTH)

AF:

0.00531

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00619

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 07, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 22, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fabry disease

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

-0.011

PromoterAI

-0.058

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over