X-101397655-C-T

Position:

• chrX-101397655-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001199973.2(RPL36A-HNRNPH2):​c.300+2198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 485,685 control chromosomes in the GnomAD database, including 2,940 homozygotes. There are 22,557 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (678 hom., 3923 hem., cov: 22)
  • Exomes 𝑓: 0.13 (2262 hom. 18634 hem.)
• Consequence: RPL36A-HNRNPH2 NM_001199973.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.467

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-101397655-C-T is Benign according to our data. Variant chrX-101397655-C-T is described in ClinVar as [Benign]. Clinvar id is 1241572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL36A-HNRNPH2	NM_001199973.2	c.300+2198C>T		intron_variant
RPL36A-HNRNPH2	NM_001199974.2	c.177+5833C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLA	ENST00000710365.1	c.*154G>A		3_prime_UTR_variant	8/8
GLA	ENST00000468823.2	n.2866G>A		non_coding_transcript_exon_variant	4/4	5
GLA	ENST00000674142.1	n.1421+327G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.126 AC: 13881 AN: 110027 Hom.: 678 Cov.: 22 AF XY: 0.121 AC XY: 3915 AN XY: 32307

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0997

GnomAD4 exome AF: 0.132 AC: 49606 AN: 375607 Hom.: 2262 AF XY: 0.145 AC XY: 18634 AN XY: 128773

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0793

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.0927

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.126 AC: 13887 AN: 110078 Hom.: 678 Cov.: 22 AF XY: 0.121 AC XY: 3923 AN XY: 32368

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0969

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0869

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.0840

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.135 Hom.: 758

Bravo AF: 0.128

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.55

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: rs35019768; hg19: chrX-100652643;