17-42910986-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The ENST00000253801.7(G6PC1):c.634A>T(p.Ile212Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. I212V) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000253801.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
G6PC1 | NM_000151.4 | c.634A>T | p.Ile212Phe | missense_variant | 5/5 | ENST00000253801.7 | NP_000142.2 | |
G6PC1 | NM_001270397.2 | c.*26A>T | 3_prime_UTR_variant | 5/5 | NP_001257326.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
G6PC1 | ENST00000253801.7 | c.634A>T | p.Ile212Phe | missense_variant | 5/5 | 1 | NM_000151.4 | ENSP00000253801 | P1 | |
G6PC1 | ENST00000585489.1 | c.*26A>T | 3_prime_UTR_variant | 4/4 | 5 | ENSP00000466202 | ||||
G6PC1 | ENST00000592383.5 | c.*26A>T | 3_prime_UTR_variant | 5/5 | 2 | ENSP00000465958 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251240Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135766
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727246
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Glycogen storage disease due to glucose-6-phosphatase deficiency type IA Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 20, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 30, 2021 | This sequence change replaces isoleucine with phenylalanine at codon 212 of the G6PC protein (p.Ile212Phe). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with G6PC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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