rs3027589

Positions:

• chrX-101400598-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000218516.4(GLA):​c.639+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 615,286 control chromosomes in the GnomAD database, including 891 homozygotes. There are 10,075 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (280 hom., 1972 hem., cov: 22)
  • Exomes 𝑓: 0.046 (611 hom. 8103 hem.)
• Consequence: GLA ENST00000218516.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.129

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]

RPL36A-HNRNPH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-101400598-T-C is Benign according to our data. Variant chrX-101400598-T-C is described in ClinVar as [Benign]. Clinvar id is 1275736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLA	NM_000169.3	c.639+68A>G		intron_variant		ENST00000218516.4	NP_000160.1
RPL36A-HNRNPH2	NM_001199973.2	c.300+5141T>C		intron_variant			NP_001186902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLA	ENST00000218516.4	c.639+68A>G		intron_variant		1	NM_000169.3	ENSP00000218516	P1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 7193 AN: 110691 Hom.: 279 Cov.: 22 AF XY: 0.0596 AC XY: 1961 AN XY: 32923

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.00874

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.00761

Gnomad MID AF: 0.0298

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0688

GnomAD4 exome AF: 0.0459 AC: 23135 AN: 504540 Hom.: 611 AF XY: 0.0496 AC XY: 8103 AN XY: 163476

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.0479

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.00971

Gnomad4 NFE exome AF: 0.0302

Gnomad4 OTH exome AF: 0.0464

GnomAD4 genome AF: 0.0650 AC: 7204 AN: 110746 Hom.: 280 Cov.: 22 AF XY: 0.0598 AC XY: 1972 AN XY: 32988

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.00874

Gnomad4 EAS AF: 0.0350

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.00761

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0679

Alfa AF: 0.0347 Hom.: 1435

Bravo AF: 0.0762

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs3027589; hg19: chrX-100655586;