chr20-34928913-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000178.4(GSS):​c.1340A>G​(p.His447Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

GSS
NM_000178.4 missense

Scores

11
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GSSNM_000178.4 linkuse as main transcriptc.1340A>G p.His447Arg missense_variant 13/13 ENST00000651619.1
GSSNM_001322494.1 linkuse as main transcriptc.1340A>G p.His447Arg missense_variant 13/13
GSSNM_001322495.1 linkuse as main transcriptc.1340A>G p.His447Arg missense_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSSENST00000651619.1 linkuse as main transcriptc.1340A>G p.His447Arg missense_variant 13/13 NM_000178.4 P1P48637-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityOct 11, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Pathogenic
0.49
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.97
.;D;D;D;.
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.89
.;.;.;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.94
D;D;D;D;D
MetaSVM
Pathogenic
0.95
D
MutationAssessor
Uncertain
2.9
.;M;M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-7.1
.;D;.;.;D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
.;D;.;.;D
Sift4G
Uncertain
0.0050
.;D;.;.;D
Polyphen
1.0
.;D;D;D;.
Vest4
0.85, 0.96
MutPred
0.77
.;Gain of MoRF binding (P = 0.0068);Gain of MoRF binding (P = 0.0068);Gain of MoRF binding (P = 0.0068);.;
MVP
0.98
MPC
0.89
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.98
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33516716; API