rs1557230370
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BS2_Supporting
The NM_001360016.2(G6PD):c.574C>T(p.Arg192Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,097,395 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. 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. R192H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001360016.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
G6PD | NM_001360016.2 | c.574C>T | p.Arg192Cys | missense_variant | 6/13 | ENST00000393562.10 | |
G6PD | NM_000402.4 | c.664C>T | p.Arg222Cys | missense_variant | 6/13 | ||
G6PD | NM_001042351.3 | c.574C>T | p.Arg192Cys | missense_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
G6PD | ENST00000393562.10 | c.574C>T | p.Arg192Cys | missense_variant | 6/13 | 1 | NM_001360016.2 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183252Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67752
GnomAD4 exome AF: 0.0000118 AC: 13AN: 1097395Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 6AN XY: 362791
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Anemia, nonspherocytic hemolytic, due to G6PD deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 192 of the G6PD protein (p.Arg192Cys). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with G6PD-related conditions. ClinVar contains an entry for this variant (Variation ID: 537706). 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 expected to disrupt G6PD 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