rs2273684
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000178.4(GSS):c.492-134A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 724,288 control chromosomes in the GnomAD database, including 80,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.51 ( 21260 hom., cov: 31)
Exomes 𝑓: 0.45 ( 59638 hom. )
Consequence
GSS
NM_000178.4 intron
NM_000178.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.53
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 20-34941963-T-G is Benign according to our data. Variant chr20-34941963-T-G is described in ClinVar as [Benign]. Clinvar id is 1224925.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GSS | NM_000178.4 | c.492-134A>C | intron_variant | ENST00000651619.1 | NP_000169.1 | |||
GSS | NM_001322494.1 | c.492-134A>C | intron_variant | NP_001309423.1 | ||||
GSS | NM_001322495.1 | c.492-134A>C | intron_variant | NP_001309424.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GSS | ENST00000651619.1 | c.492-134A>C | intron_variant | NM_000178.4 | ENSP00000498303.1 |
Frequencies
GnomAD3 genomes AF: 0.511 AC: 77595AN: 151814Hom.: 21236 Cov.: 31
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GnomAD4 exome AF: 0.445 AC: 254943AN: 572356Hom.: 59638 AF XY: 0.447 AC XY: 139999AN XY: 312902
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GnomAD4 genome AF: 0.511 AC: 77648AN: 151932Hom.: 21260 Cov.: 31 AF XY: 0.508 AC XY: 37730AN XY: 74252
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at