rs201700844
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_138387.4(G6PC3):āc.800C>Gā(p.Ser267Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000906 in 1,611,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_138387.4 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 | UniProt |
---|---|---|---|---|---|---|---|
G6PC3 | NM_138387.4 | c.800C>G | p.Ser267Cys | missense_variant | 6/6 | ENST00000269097.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
G6PC3 | ENST00000269097.9 | c.800C>G | p.Ser267Cys | missense_variant | 6/6 | 1 | NM_138387.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249590Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135128
GnomAD4 exome AF: 0.0000856 AC: 125AN: 1459498Hom.: 0 Cov.: 33 AF XY: 0.0000964 AC XY: 70AN XY: 726202
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152352Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74498
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 22, 2021 | - - |
Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 267 of the G6PC3 protein (p.Ser267Cys). This variant is present in population databases (rs201700844, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with G6PC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 570187). 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