rs727504689
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate
The NM_000169.3(GLA):c.178C>T(p.Pro60Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P60L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000169.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.178C>T | p.Pro60Ser | missense_variant | 1/7 | ENST00000218516.4 | |
RPL36A-HNRNPH2 | NM_001199973.2 | c.301-4210G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.178C>T | p.Pro60Ser | missense_variant | 1/7 | 1 | NM_000169.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Fabry disease Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Nov 12, 2021 | The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. It is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In addition, In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.802; 3Cnet; 0.978). Therefore, this variant was classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.