chrX-101397549-C-T

Position:

• chrX-101397549-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001199973.2(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 NM_001199973.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.08

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=-0.97).
• 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 male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL36A-HNRNPH2	NM_001199973.2	c.300+2092C>T		intron_variant
RPL36A-HNRNPH2	NM_001199974.2	c.177+5727C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLA	ENST00000710365.1	c.*260G>A		3_prime_UTR_variant	8/8
GLA	ENST00000468823.2	n.2972G>A		non_coding_transcript_exon_variant	4/4	5
GLA	ENST00000674142.1	n.1421+433G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00827 AC: 787 AN: 95150 Hom.: 7 Cov.: 20 AF XY: 0.00640 AC XY: 156 AN XY: 24388

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

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.00277

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000390

Gnomad4 OTH AF: 0.00529

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.61

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: rs140006150; hg19: chrX-100652537;