rs869312136

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_000169.3(GLA):​c.98A>G​(p.Asp33Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic,drug response (no stars).

Frequency

Genomes: not found (cov: 23)

Consequence

GLA
NM_000169.3 missense

Scores

6
9
3

Clinical Significance

Pathogenic; drug response no assertion criteria provided P:1O:1

Conservation

PhyloP100: 5.95
Variant links:
Genes affected
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874
PP5
Variant X-101407806-T-C is Pathogenic according to our data. Variant chrX-101407806-T-C is described in ClinVar as [Pathogenic, drug_response]. Clinvar id is 217375.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GLANM_000169.3 linkuse as main transcriptc.98A>G p.Asp33Gly missense_variant 1/7 ENST00000218516.4 NP_000160.1 P06280Q53Y83

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GLAENST00000218516.4 linkuse as main transcriptc.98A>G p.Asp33Gly missense_variant 1/71 NM_000169.3 ENSP00000218516.4 P06280
RPL36A-HNRNPH2ENST00000409170.3 linkuse as main transcriptc.301-4130T>C intron_variant 4 ENSP00000386655.4 H7BZ11

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic; drug response
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Fabry disease Pathogenic:1
Pathogenic, no assertion criteria providedresearchAlbrecht-Kossel-Institute, Medical University RostockJan 01, 2014- -
Migalastat response Other:1
drug response, no assertion criteria providedresearchAlbrecht-Kossel-Institute, Medical University RostockJan 01, 2014- Pharmacological Chaperone response: yes

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
CardioboostCm
Uncertain
0.19
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D;.
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Pathogenic
0.93
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Uncertain
0.77
D
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-4.2
D;.
REVEL
Pathogenic
0.75
Sift
Uncertain
0.0020
D;.
Sift4G
Uncertain
0.0040
D;.
Polyphen
0.64
P;.
Vest4
0.79
MutPred
0.57
Gain of methylation at R38 (P = 0.0395);Gain of methylation at R38 (P = 0.0395);
MVP
0.97
MPC
1.7
ClinPred
0.99
D
GERP RS
5.5
Varity_R
0.90
gMVP
0.95

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.

Other links and lift over

dbSNP: rs869312136; hg19: chrX-100662794; API