rs780358808
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000294.3(PHKG2):c.907A>C(p.Thr303Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. T303A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000294.3 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 |
---|---|---|---|---|---|---|---|
PHKG2 | NM_000294.3 | c.907A>C | p.Thr303Pro | missense_variant | 9/10 | ENST00000563588.6 | |
PHKG2 | NM_001172432.2 | c.907A>C | p.Thr303Pro | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKG2 | ENST00000563588.6 | c.907A>C | p.Thr303Pro | missense_variant | 9/10 | 1 | NM_000294.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250844Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135708
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461748Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727170
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Glycogen storage disease IXc Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces threonine with proline at codon 303 of the PHKG2 protein (p.Thr303Pro). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and proline. This variant is present in population databases (rs780358808, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with PHKG2-related conditions. 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 PHKG2 protein function. 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