rs1555985827
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000169.3(GLA):c.456C>T(p.Tyr152Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,093,816 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )
Consequence
GLA
NM_000169.3 synonymous
NM_000169.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0430
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant X-101401723-G-A is Benign according to our data. Variant chrX-101401723-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1097822.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-101401723-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.043 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.456C>T | p.Tyr152Tyr | synonymous_variant | 3/7 | ENST00000218516.4 | NP_000160.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.456C>T | p.Tyr152Tyr | synonymous_variant | 3/7 | 1 | NM_000169.3 | ENSP00000218516.4 | ||
RPL36A-HNRNPH2 | ENST00000409170.3 | c.300+6266G>A | intron_variant | 4 | ENSP00000386655.4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome AF: 0.00000457 AC: 5AN: 1093816Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 1AN XY: 359326
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1
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359326
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GnomAD4 genome Cov.: 23
GnomAD4 genome
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23
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fabry disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 13, 2023 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at