Variant X-101397760-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001199973.2(RPL36A-HNRNPH2):c.300+2303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000478 in 1,073,728 control chromosomes in the GnomAD database, including 3 homozygotes. There are 141 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., 80 hem., cov: 23)

Exomes 𝑓: 0.00024 ( 3 hom. 61 hem. )

Consequence

RPL36A-HNRNPH2
NM_001199973.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.140

Variant links:

Genes affected

RPL36A-HNRNPH2 (HGNC:):

RPL36A-HNRNPH2 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-101397760-T-C is Benign according to our data. Variant chrX-101397760-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1187221.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 80 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL36A-HNRNPH2	NM_001199973.2 linkuse as main transcript	c.300+2303T>C		intron_variant
GLA	NM_000169.3 linkuse as main transcript			downstream_gene_variant		ENST00000218516.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLA	ENST00000218516.4 linkuse as main transcript			downstream_gene_variant		1	NM_000169.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

278

AN:

112591

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

AN XY:

34783

show subpopulations

Gnomad AFR

AF:

0.00739

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00329

GnomAD3 exomes

AF:

0.000674

AC:

120

AN:

177962

Hom.:

AF XY:

0.000418

AC XY:

AN XY:

64660

show subpopulations

Gnomad AFR exome

AF:

0.00823

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000129

Gnomad OTH exome

AF:

0.000678

GnomAD4 exome

AF:

0.000245

AC:

235

AN:

961087

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

AN XY:

278511

show subpopulations

Gnomad4 AFR exome

AF:

0.00739

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000696

Gnomad4 OTH exome

AF:

0.000602

GnomAD4 genome

AF:

0.00247

AC:

278

AN:

112641

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

AN XY:

34843

show subpopulations

Gnomad4 AFR

AF:

0.00737

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00325

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00349

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.61

DANN

Benign

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over