X-101397534-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001199973.2(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 NM_001199973.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.530

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 -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/exons	MANE	UniProt
RPL36A-HNRNPH2	NM_001199973.2	c.300+2077C>T		intron_variant
RPL36A-HNRNPH2	NM_001199974.2	c.177+5712C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLA	ENST00000710365.1	c.*275G>A		3_prime_UTR_variant	8/8
GLA	ENST00000468823.2	n.2987G>A		non_coding_transcript_exon_variant	4/4	5
GLA	ENST00000674142.1	n.1421+448G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 6243 AN: 101401 Hom.: 598 Cov.: 20 AF XY: 0.0425 AC XY: 1098 AN XY: 25845

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

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.000386

Gnomad4 EAS AF: 0.00180

Gnomad4 SAS AF: 0.00184

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.0528

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.8
Dann	Benign	0.34

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: rs146101947; hg19: chrX-100652522;