rs2071225

Variant names:

Variant summary

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

The NM_000169.3(GLA):c.-10C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 1,201,243 control chromosomes in the GnomAD database, including 2,804 homozygotes. There are 31,097 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 208 hom., 2527 hem., cov: 23)

Exomes 𝑓: 0.074 ( 2596 hom. 28570 hem. )

Consequence

GLA
NM_000169.3 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:19

Conservation

PhyloP100: -0.554

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant X-101407913-G-A is Benign according to our data. Variant chrX-101407913-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 36280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-101407913-G-A is described in Lovd as [Benign]. Variant chrX-101407913-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLA	NM_000169.3 link	c.-10C>T		5_prime_UTR_variant	Exon 1 of 7	ENST00000218516.4	NP_000160.1	P06280Q53Y83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLA	ENST00000218516.4 link	c.-10C>T		5_prime_UTR_variant	Exon 1 of 7	1	NM_000169.3	ENSP00000218516.4		P06280
RPL36A-HNRNPH2	ENST00000409170.3 link	c.301-4023G>A		intron_variant	Intron 4 of 4	4		ENSP00000386655.4		H7BZ11

Frequencies

GnomAD3 genomes

AF:

0.0700

AC:

7839

AN:

111984

Hom.:

209

Cov.:

AF XY:

0.0739

AC XY:

2524

AN XY:

34166

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.0968

Gnomad AMR

AF:

0.0730

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0793

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.0641

Gnomad MID

AF:

0.0462

Gnomad NFE

AF:

0.0611

Gnomad OTH

AF:

0.0677

GnomAD3 exomes

AF:

0.0932

AC:

17056

AN:

182908

Hom.:

754

AF XY:

0.0995

AC XY:

6711

AN XY:

67418

show subpopulations

Gnomad AFR exome

AF:

0.0670

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.0510

Gnomad EAS exome

AF:

0.0768

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.0633

Gnomad NFE exome

AF:

0.0590

Gnomad OTH exome

AF:

0.0816

GnomAD4 exome

AF:

0.0736

AC:

80193

AN:

1089205

Hom.:

2596

Cov.:

AF XY:

0.0804

AC XY:

28570

AN XY:

355297

show subpopulations

Gnomad4 AFR exome

AF:

0.0712

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.0781

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.0645

Gnomad4 NFE exome

AF:

0.0603

Gnomad4 OTH exome

AF:

0.0785

GnomAD4 genome

AF:

0.0699

AC:

7833

AN:

112038

Hom.:

208

Cov.:

AF XY:

0.0738

AC XY:

2527

AN XY:

34230

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.0731

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.0792

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.0641

Gnomad4 NFE

AF:

0.0611

Gnomad4 OTH

AF:

0.0682

Alfa

AF:

0.0632

Hom.:

646

Bravo

AF:

0.0696

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:19

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Jan 12, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

-10C>T in 5'UTR of GLA: This variant is not expected to have clinical significan ce because it has been identified in 6.7% (256/3835) of African American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS/; dbSNP rs2071225). -10C>T in 5'UTR of GLA (rs2071225; all ele frequency = 6.7%, 256/3835) ** -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

Mar 06, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:6

Jun 19, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 15, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 14, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21092187, 21896204, 18979223, 26981927, 25281798, 26334996, 25772321, 23677059, 22682330, 21683120, 8411052, 26070511, 29794742, 31996269) -

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 01, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Fabry disease

Benign:5

Mar 19, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Cardiomyopathy

Benign:1

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

-0.60

CADD

Benign

4.3

DANN

Benign

0.79

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