X-101397565-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001199973.2(RPL36A-HNRNPH2):c.300+2113dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (3030 hom., 3929 hem., cov: 16)
• Consequence: RPL36A-HNRNPH2 NM_001199973.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

Genes affected

RPL36A-HNRNPH2 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-101397565-G-GC is Benign according to our data. Variant chrX-101397565-G-GC is described in ClinVar as [Benign]. Clinvar id is 1293345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL36A-HNRNPH2	NM_001199973.2	c.300+2113dup		intron_variant
RPL36A-HNRNPH2	NM_001199974.2	c.177+5748dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLA	ENST00000710365.1	c.*243_*244insG		3_prime_UTR_variant	8/8
GLA	ENST00000468823.2	n.2955_2956insG		non_coding_transcript_exon_variant	4/4	5
GLA	ENST00000674142.1	n.1421+416_1421+417insG		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.165 AC: 17552 AN: 106321 Hom.: 3026 Cov.: 16 AF XY: 0.134 AC XY: 3908 AN XY: 29193

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.0104

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.00727

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.00764

Gnomad MID AF: 0.0487

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 17582 AN: 106359 Hom.: 3030 Cov.: 16 AF XY: 0.134 AC XY: 3929 AN XY: 29245

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.00727

Gnomad4 EAS AF: 0.0383

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.00764

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.144

Alfa AF: 0.125 Hom.: 687

Bravo AF: 0.198

Asia WGS AF: 0.143 AC: 362 AN: 2522

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs200620191; hg19: chrX-100652553;