chr20-34928738-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000178.4(GSS):c.*90A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,445,878 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0051 ( 8 hom., cov: 31)
Exomes 𝑓: 0.00073 ( 8 hom. )
Consequence
GSS
NM_000178.4 3_prime_UTR
NM_000178.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.643
Genes affected
GSS (HGNC:4624): (glutathione synthetase) Glutathione is important for a variety of biological functions, including protection of cells from oxidative damage by free radicals, detoxification of xenobiotics, and membrane transport. The protein encoded by this gene functions as a homodimer to catalyze the second step of glutathione biosynthesis, which is the ATP-dependent conversion of gamma-L-glutamyl-L-cysteine to glutathione. Defects in this gene are a cause of glutathione synthetase deficiency. [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=-0.91).
BP6
Variant 20-34928738-T-C is Benign according to our data. Variant chr20-34928738-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 338290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00514 (782/152026) while in subpopulation AFR AF= 0.018 (746/41438). AF 95% confidence interval is 0.0169. There are 8 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSS | NM_000178.4 | c.*90A>G | 3_prime_UTR_variant | 13/13 | ENST00000651619.1 | ||
GSS | NM_001322494.1 | c.*90A>G | 3_prime_UTR_variant | 13/13 | |||
GSS | NM_001322495.1 | c.*90A>G | 3_prime_UTR_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSS | ENST00000651619.1 | c.*90A>G | 3_prime_UTR_variant | 13/13 | NM_000178.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00514 AC: 781AN: 151908Hom.: 8 Cov.: 31
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GnomAD4 exome AF: 0.000729 AC: 943AN: 1293852Hom.: 8 Cov.: 19 AF XY: 0.000612 AC XY: 398AN XY: 650448
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GnomAD4 genome AF: 0.00514 AC: 782AN: 152026Hom.: 8 Cov.: 31 AF XY: 0.00501 AC XY: 372AN XY: 74304
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2021 | See Variant Classification Assertion Criteria. - |
Inherited glutathione synthetase deficiency Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at