ENST00000409170.3:c.300+2092C>T

Variant names:

• chrX-101397549-C-T
• rs140006150
• ENST00000409170.3:c.300+2092C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000409170.3(RPL36A-HNRNPH2):​c.300+2092C>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 Likely benign (★).

• Frequency: Genomes: 𝑓 0.0083 (7 hom., 155 hem., cov: 20)
• Consequence: RPL36A-HNRNPH2 ENST00000409170.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.08
• 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=-0.97).
• BP6: Variant X-101397549-C-T is Benign according to our data. Variant chrX-101397549-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1202191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00829 (789/95171) while in subpopulation AFR AF = 0.0383 (752/19641). AF 95% confidence interval is 0.036. There are 7 homozygotes in GnomAd4. There are 155 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL36A-HNRNPH2	NM_001199973.2	c.300+2092C>T		intron_variant	Intron 4 of 4		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.177+5727C>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+2092C>T		intron_variant	Intron 4 of 4	4		ENSP00000386655.4

Frequencies

GnomAD3 genomes AF: 0.00827 AC: 787 AN: 95150 Hom.: 7 Cov.: 20

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00277

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0146

Gnomad NFE AF: 0.0000390

Gnomad OTH AF: 0.00536

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

GnomAD4 genome AF: 0.00829 AC: 789 AN: 95171 Hom.: 7 Cov.: 20 AF XY: 0.00635 AC XY: 155 AN XY: 24417

African (AFR) AF: 0.0383 AC: 752 AN: 19641

American (AMR) AF: 0.00277 AC: 25 AN: 9026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2584

East Asian (EAS) AF: 0.00 AC: 0 AN: 3256

South Asian (SAS) AF: 0.00 AC: 0 AN: 2073

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5087

Middle Eastern (MID) AF: 0.0155 AC: 3 AN: 193

European-Non Finnish (NFE) AF: 0.0000390 AC: 2 AN: 51331

Other (OTH) AF: 0.00529 AC: 7 AN: 1323

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 27, 2018

GeneDx

Significance: Likely 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	-0.97
CADD	Benign	0.52
DANN	Benign	0.61
PhyloP100		-3.1

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: rs140006150; hg19: chrX-100652537;