X-101397565-G-GC

Variant names:

• chrX-101397565-G-GC
• rs200620191
• ENST00000409170.3:c.300+2113dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000409170.3(RPL36A-HNRNPH2):​c.300+2113dupC 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 ENST00000409170.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40
• Publications: 0 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• Fabry disease

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GLA	NM_000169.3	c.*243dupG		downstream_gene_variant		ENST00000218516.4	NP_000160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL36A-HNRNPH2	ENST00000409170.3	c.300+2113dupC		intron_variant	Intron 4 of 4	4		ENSP00000386655.4
GLA	ENST00000218516.4	c.*243dupG		downstream_gene_variant		1	NM_000169.3	ENSP00000218516.4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 17552 AN: 106321 Hom.: 3026 Cov.: 16

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

African (AFR) AF: 0.506 AC: 14296 AN: 28231

American (AMR) AF: 0.123 AC: 1206 AN: 9819

Ashkenazi Jewish (ASJ) AF: 0.00727 AC: 19 AN: 2614

East Asian (EAS) AF: 0.0383 AC: 130 AN: 3390

South Asian (SAS) AF: 0.108 AC: 256 AN: 2362

European-Finnish (FIN) AF: 0.00764 AC: 41 AN: 5365

Middle Eastern (MID) AF: 0.0534 AC: 11 AN: 206

European-Non Finnish (NFE) AF: 0.0270 AC: 1409 AN: 52262

Other (OTH) AF: 0.144 AC: 207 AN: 1440

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

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs200620191; hg19: chrX-100652553;