rs2230036
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001360016.2(G6PD):c.1116G>A(p.Gln372=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,210,729 control chromosomes in the GnomAD database, including 260 homozygotes. There are 1,981 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.032 ( 141 hom., 965 hem., cov: 24)
Exomes 𝑓: 0.0034 ( 119 hom. 1016 hem. )
Consequence
G6PD
NM_001360016.2 synonymous
NM_001360016.2 synonymous
Scores
2
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant X-154532738-C-T is Benign according to our data. Variant chrX-154532738-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 10365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
G6PD | NM_001360016.2 | c.1116G>A | p.Gln372= | synonymous_variant | 10/13 | ENST00000393562.10 | |
G6PD | NM_000402.4 | c.1206G>A | p.Gln402= | synonymous_variant | 10/13 | ||
G6PD | NM_001042351.3 | c.1116G>A | p.Gln372= | synonymous_variant | 10/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
G6PD | ENST00000393562.10 | c.1116G>A | p.Gln372= | synonymous_variant | 10/13 | 1 | NM_001360016.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0314 AC: 3549AN: 112977Hom.: 137 Cov.: 24 AF XY: 0.0272 AC XY: 956AN XY: 35129
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GnomAD3 exomes AF: 0.00888 AC: 1607AN: 181037Hom.: 66 AF XY: 0.00537 AC XY: 354AN XY: 65903
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GnomAD4 exome AF: 0.00337 AC: 3703AN: 1097698Hom.: 119 Cov.: 33 AF XY: 0.00280 AC XY: 1016AN XY: 363152
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GnomAD4 genome ? AF: 0.0315 AC: 3565AN: 113031Hom.: 141 Cov.: 24 AF XY: 0.0274 AC XY: 965AN XY: 35193
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 16, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | G6PD: BP4 - |
Anemia, nonspherocytic hemolytic, due to G6PD deficiency Benign:2
Benign, criteria provided, single submitter | curation | Dunham Lab, University of Washington | Aug 12, 2022 | Variant found in over 150 individuals without G6PD deficiency (BS2) and the activity in red blood cells is within the normal range (BS3). Previously interpreted as bening (BP6). Post_P 0.00015 (odds of pathogenicity 0.0014, Prior_P 0.1). - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
G6PD deficiency Benign:2
Benign, no assertion criteria provided | literature only | OMIM | Aug 26, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 01, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at