chrX-154536032-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001360016.2(G6PD):c.172G>A(p.Asp58Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,456 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
G6PD
NM_001360016.2 missense
NM_001360016.2 missense
Scores
5
5
3
Clinical Significance
Conservation
PhyloP100: 7.41
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 6 ACMG points.
PM1
In a hotspot region, there are 8 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_001360016.2
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.919
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
G6PD | NM_001360016.2 | c.172G>A | p.Asp58Asn | missense_variant | 4/13 | ENST00000393562.10 | |
G6PD | NM_000402.4 | c.262G>A | p.Asp88Asn | missense_variant | 4/13 | ||
G6PD | NM_001042351.3 | c.172G>A | p.Asp58Asn | missense_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
G6PD | ENST00000393562.10 | c.172G>A | p.Asp58Asn | missense_variant | 4/13 | 1 | NM_001360016.2 | P4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097456Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 362818
GnomAD4 exome
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1
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31
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0
AN XY:
362818
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Anemia, nonspherocytic hemolytic, due to G6PD deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | curation | Dunham Lab, University of Washington | Aug 12, 2022 | Variant found in unrelated hemizygotes with deficiency (PP4, PS4_M). Phenotype transmits with phenotype from mother to son (PP1). Decreased activity in red blood cells (12-39%) (PS3). Not found in gnomAD (PM2). Post_P 0.994 (odds of pathogenicity 1517, Prior_P 0.1). - |
G6PD METAPONTO Other:1
other, no assertion criteria provided | literature only | OMIM | May 24, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;.;D;.;D
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
M;M;M;M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;.;T;T;.;.;.
Polyphen
D;D;D;.;.;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);Gain of MoRF binding (P = 0.0681);
MVP
MPC
0.70
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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