rs137852318
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001360016.2(G6PD):c.844G>T(p.Asp282Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 24)
Consequence
G6PD
NM_001360016.2 missense
NM_001360016.2 missense
Scores
11
5
1
Clinical Significance
Conservation
PhyloP100: 4.62
Genes affected
G6PD (HGNC:4057): (glucose-6-phosphate dehydrogenase) This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.967
PP5
Variant X-154533596-C-A is Pathogenic according to our data. Variant chrX-154533596-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1722591.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154533596-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
G6PD | NM_001360016.2 | c.844G>T | p.Asp282Tyr | missense_variant | 8/13 | ENST00000393562.10 | NP_001346945.1 | |
G6PD | NM_000402.4 | c.934G>T | p.Asp312Tyr | missense_variant | 8/13 | NP_000393.4 | ||
G6PD | NM_001042351.3 | c.844G>T | p.Asp282Tyr | missense_variant | 8/13 | NP_001035810.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
G6PD | ENST00000393562.10 | c.844G>T | p.Asp282Tyr | missense_variant | 8/13 | 1 | NM_001360016.2 | ENSP00000377192.3 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
Cov.:
24
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 24
GnomAD4 genome
Cov.:
24
Bravo
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Anemia, nonspherocytic hemolytic, due to G6PD deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | curation | Dunham Lab, University of Washington | Aug 12, 2022 | Variant found in hemizygote with G6PD deficiency (PP4). Heterozygous mother and sister also have deficiency (PP1). Decreased activity in red blood cells (PS3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.975 (odds of pathogenicity 350.3, Prior_P 0.1). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;.;D;.
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;H;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
.;.;D;D;D;D
Sift4G
Uncertain
D;.;D;D;.;.
Polyphen
D;D;D;.;.;.
Vest4
MutPred
Gain of phosphorylation at D282 (P = 0.0274);Gain of phosphorylation at D282 (P = 0.0274);Gain of phosphorylation at D282 (P = 0.0274);.;.;.;
MVP
MPC
2.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at