X-101397534-C-T

Variant names:

• chrX-101397534-C-T
• rs146101947
• ENST00000409170.3:c.300+2077C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000409170.3(RPL36A-HNRNPH2):​c.300+2077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (600 hom., 1104 hem., cov: 20)
• Consequence: RPL36A-HNRNPH2 ENST00000409170.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.530
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-101397534-C-T is Benign according to our data. Variant chrX-101397534-C-T is described in ClinVar as [Benign]. Clinvar id is 1178497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL36A-HNRNPH2	NM_001199973.2	c.300+2077C>T		intron_variant	Intron 4 of 4		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.177+5712C>T		intron_variant	Intron 3 of 3		NP_001186903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL36A-HNRNPH2	ENST00000409170.3	c.300+2077C>T		intron_variant	Intron 4 of 4	4		ENSP00000386655.4

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 6243 AN: 101401 Hom.: 598 Cov.: 20

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.000386

Gnomad EAS AF: 0.00209

Gnomad SAS AF: 0.00137

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0185

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0468

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

GnomAD4 genome AF: 0.0617 AC: 6256 AN: 101426 Hom.: 600 Cov.: 20 AF XY: 0.0427 AC XY: 1104 AN XY: 25882

African (AFR) AF: 0.237 AC: 5902 AN: 24919

American (AMR) AF: 0.0222 AC: 208 AN: 9366

Ashkenazi Jewish (ASJ) AF: 0.000386 AC: 1 AN: 2588

East Asian (EAS) AF: 0.00180 AC: 6 AN: 3336

South Asian (SAS) AF: 0.00184 AC: 4 AN: 2176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5205

Middle Eastern (MID) AF: 0.0155 AC: 3 AN: 194

European-Non Finnish (NFE) AF: 0.00116 AC: 60 AN: 51612

Other (OTH) AF: 0.0528 AC: 72 AN: 1363

Alfa AF: 0.0509 Hom.: 155

Bravo AF: 0.0762

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

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	-0.90
CADD	Benign	2.8
DANN	Benign	0.34
PhyloP100		0.53

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: rs146101947; hg19: chrX-100652522;