rs76910485
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000157.4(GBA1):c.1289C>T(p.Pro430Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P430P) has been classified as Likely benign.
Frequency
Consequence
NM_000157.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GBA1 | NM_000157.4 | c.1289C>T | p.Pro430Leu | missense_variant | 9/11 | ENST00000368373.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GBA1 | ENST00000368373.8 | c.1289C>T | p.Pro430Leu | missense_variant | 9/11 | 1 | NM_000157.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2020 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects GBA protein function (PMID: 15146461,11259172). This variant has been observed in individual(s) with Gaucher disease (PMID: 15146461,11259172). This variant is also known as P391L (c.1289C>T). ClinVar contains an entry for this variant (Variation ID: 931820). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 430 of the GBA protein (p.Pro430Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. - |
Gaucher disease perinatal lethal Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Sep 28, 2018 | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: BP5,PP5,PP3,PP2,PM1,PM2,PS3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at