20-34928900-G-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000178.4(GSS):āc.1353C>Gā(p.Thr451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,670 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 (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
GSS
NM_000178.4 synonymous
NM_000178.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.30
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 20-34928900-G-C is Benign according to our data. Variant chr20-34928900-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2893658.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.3 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSS | NM_000178.4 | c.1353C>G | p.Thr451= | synonymous_variant | 13/13 | ENST00000651619.1 | |
GSS | NM_001322494.1 | c.1353C>G | p.Thr451= | synonymous_variant | 13/13 | ||
GSS | NM_001322495.1 | c.1353C>G | p.Thr451= | synonymous_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSS | ENST00000651619.1 | c.1353C>G | p.Thr451= | synonymous_variant | 13/13 | NM_000178.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250856Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135664
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461670Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727132
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GnomAD4 genome Cov.: 31
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inherited glutathione synthetase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 20, 2023 | - - |
Computational scores
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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