rs202007119
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The NM_000404.4(GLB1):c.1481G>T(p.Gly494Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G494C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000404.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLB1 | NM_000404.4 | c.1481G>T | p.Gly494Val | missense_variant, splice_region_variant | 15/16 | ENST00000307363.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLB1 | ENST00000307363.10 | c.1481G>T | p.Gly494Val | missense_variant, splice_region_variant | 15/16 | 1 | NM_000404.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000814 AC: 2AN: 245800Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133554
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461456Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 726968
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74456
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-IV-B;C0268271:Infantile GM1 gangliosidosis;C0268272:GM1 gangliosidosis type 2;C0268273:GM1 gangliosidosis type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 19, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at