rs183596463
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_152281.3(GORAB):c.658G>A(p.Ala220Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,607,844 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A220P) has been classified as Pathogenic.
Frequency
Consequence
NM_152281.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GORAB | NM_152281.3 | c.658G>A | p.Ala220Thr | missense_variant | 4/5 | ENST00000367763.8 | NP_689494.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GORAB | ENST00000367763.8 | c.658G>A | p.Ala220Thr | missense_variant | 4/5 | 2 | NM_152281.3 | ENSP00000356737.4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250936Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135622
GnomAD4 exome AF: 0.0000199 AC: 29AN: 1455702Hom.: 0 Cov.: 31 AF XY: 0.0000194 AC XY: 14AN XY: 723038
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2021 | The c.733G>A (p.A245T) alteration is located in exon 4 (coding exon 4) of the GORAB gene. This alteration results from a G to A substitution at nucleotide position 733, causing the alanine (A) at amino acid position 245 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Geroderma osteodysplastica Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 24, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 245 of the GORAB protein (p.Ala245Thr). This variant is present in population databases (rs183596463, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GORAB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at