rs381427
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PS1_ModeratePM1PM2PM5PP3PP5_Moderate
The NM_000157.4(GBA1):c.689T>G(p.Val230Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V230E) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000157.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GBA1 | NM_000157.4 | c.689T>G | p.Val230Gly | missense_variant | 6/11 | ENST00000368373.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GBA1 | ENST00000368373.8 | c.689T>G | p.Val230Gly | missense_variant | 6/11 | 1 | NM_000157.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151988Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251390Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135868
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727216
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151988Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74230
ClinVar
Submissions by phenotype
Gaucher disease Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 28, 2024 | Variant summary: GBA1 c.689T>G (p.Val230Gly) results in a non-conservative amino acid change located in the TIM-barrel domain (IPR033453) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.6e-06 in 1606838 control chromosomes. c.689T>G has been reported in the literature in multiple individuals affected with Gaucher Disease. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. ClinVar contains an entry for this variant (Variation ID: 928835). Based on the evidence outlined above, the variant was classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at