8-30679589-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_000637.5(GSR):c.1500G>A(p.Thr500=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
GSR
NM_000637.5 synonymous
NM_000637.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.458
Genes affected
GSR (HGNC:4623): (glutathione-disulfide reductase) This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. This enzyme is a homodimeric flavoprotein. It is a central enzyme of cellular antioxidant defense, and reduces oxidized glutathione disulfide (GSSG) to the sulfhydryl form GSH, which is an important cellular antioxidant. Rare mutations in this gene result in hereditary glutathione reductase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 8-30679589-C-T is Benign according to our data. Variant chr8-30679589-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 771424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.458 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSR | NM_000637.5 | c.1500G>A | p.Thr500= | synonymous_variant | 13/13 | ENST00000221130.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSR | ENST00000221130.11 | c.1500G>A | p.Thr500= | synonymous_variant | 13/13 | 1 | NM_000637.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000493 AC: 124AN: 251476Hom.: 0 AF XY: 0.000449 AC XY: 61AN XY: 135920
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GnomAD4 exome AF: 0.000159 AC: 232AN: 1461788Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 118AN XY: 727222
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
GSR-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 19, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hemolytic anemia due to glutathione reductase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 13, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 13, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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