rs146101947

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-101397534-C-A
• chrX-101397534-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001199973.2(RPL36A-HNRNPH2):​c.300+2077C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 20)
• Consequence: RPL36A-HNRNPH2 NM_001199973.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL36A-HNRNPH2	NM_001199973.2		c.300+2077C>A		intron	N/A	NP_001186902.2	H7BZ11
	RPL36A-HNRNPH2	NM_001199974.2		c.177+5712C>A		intron	N/A	NP_001186903.2	H0Y3V9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL36A-HNRNPH2	ENST00000409170.3	TSL:4	c.300+2077C>A		intron	N/A	ENSP00000386655.4	H7BZ11
	GLA	ENST00000710365.1		c.*275G>T		3_prime_UTR	Exon 8 of 8	ENSP00000518234.1	A0AA34QW02
	RPL36A-HNRNPH2	ENST00000409338.5	TSL:4	c.177+5712C>A		intron	N/A	ENSP00000386974.2	H0Y3V9

Frequencies

GnomAD3 genomes Cov.: 20

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

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.35
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;