rs34193178
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM1BP4_ModerateBS2_Supporting
The NM_001360016.2(G6PD):āc.1048G>Cā(p.Asp350His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,210,701 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 63 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001360016.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
G6PD | NM_001360016.2 | c.1048G>C | p.Asp350His | missense_variant | 9/13 | ENST00000393562.10 | |
G6PD | NM_000402.4 | c.1138G>C | p.Asp380His | missense_variant | 9/13 | ||
G6PD | NM_001042351.3 | c.1048G>C | p.Asp350His | missense_variant | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
G6PD | ENST00000393562.10 | c.1048G>C | p.Asp350His | missense_variant | 9/13 | 1 | NM_001360016.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00103 AC: 116AN: 112465Hom.: 0 Cov.: 24 AF XY: 0.000924 AC XY: 32AN XY: 34621
GnomAD3 exomes AF: 0.000399 AC: 73AN: 182804Hom.: 0 AF XY: 0.000252 AC XY: 17AN XY: 67436
GnomAD4 exome AF: 0.000124 AC: 136AN: 1098182Hom.: 0 Cov.: 33 AF XY: 0.0000853 AC XY: 31AN XY: 363554
GnomAD4 genome ? AF: 0.00103 AC: 116AN: 112519Hom.: 0 Cov.: 24 AF XY: 0.000923 AC XY: 32AN XY: 34685
ClinVar
Submissions by phenotype
not provided Pathogenic:1Benign:2
Pathogenic, flagged submission | clinical testing | Eurofins Ntd Llc (ga) | May 13, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 13, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | G6PD: BS2 - |
Anemia, nonspherocytic hemolytic, due to G6PD deficiency Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 19, 2023 | - - |
G6PD deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 12, 2022 | Variant summary: G6PD c.1138G>C (p.Asp380His) results in a non-conservative amino acid change located in the Glucose-6-phosphate dehydrogenase, C-terminal domain (IPR022675) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00046 in 204594 control chromosomes, including 23 hemizygotes (gnomAD). c.1138G>C, also known as the "Mira d'Aire" variant, has been reported in the literature in individuals affected with Glucose 6 Phosphate Dehydrogenase Deficiency (e.g. Bulliamy_1997, Manco_2007, Powers_2018). These reports do not provide unequivocal conclusions about association of the variant with Glucose 6 Phosphate Dehydrogenase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance and three as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at