2-27497355-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001486.4(GCKR):c.172G>A(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001486.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCKR | NM_001486.4 | c.172G>A | p.Ala58Thr | missense_variant | 2/19 | ENST00000264717.7 | |
GCKR | XM_011532763.1 | c.172G>A | p.Ala58Thr | missense_variant | 2/13 | ||
GCKR | XR_001738699.1 | n.238G>A | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCKR | ENST00000264717.7 | c.172G>A | p.Ala58Thr | missense_variant | 2/19 | 1 | NM_001486.4 | P1 | |
GCKR | ENST00000472290.1 | n.194G>A | non_coding_transcript_exon_variant | 2/11 | 1 | ||||
GCKR | ENST00000453813.1 | c.88G>A | p.Ala30Thr | missense_variant | 1/8 | 3 | |||
GCKR | ENST00000417872.5 | n.229G>A | non_coding_transcript_exon_variant | 2/7 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251490Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135920
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727242
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2023 | Does not currently meet published gene-disease clinical validity criteria Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 23, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GCKR protein function. ClinVar contains an entry for this variant (Variation ID: 2547744). This variant has not been reported in the literature in individuals affected with GCKR-related conditions. This variant is present in population databases (rs777420998, gnomAD 0.05%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 58 of the GCKR protein (p.Ala58Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at