chr20-23985887-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_178311.3(GGTLC1):c.392C>T(p.Thr131Met) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,611,926 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
GGTLC1
NM_178311.3 missense
NM_178311.3 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 6.79
Genes affected
GGTLC1 (HGNC:16437): (gamma-glutamyltransferase light chain 1) This gene encodes a member of the gamma-glutamyl transpeptidase (GGT) family, which are important in the metabolism of glutathione. The most ubiquitously expressed human GGT gene, GGT1, encodes a single transmembrane polypeptide that is post-translationally processed to form a heavy and a light chain. In contrast, the product of this gene only contains homology to the light chain region, and lacks a transmembrane domain. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06325391).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GGTLC1 | NM_178311.3 | c.392C>T | p.Thr131Met | missense_variant | 4/6 | ENST00000335694.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GGTLC1 | ENST00000335694.4 | c.392C>T | p.Thr131Met | missense_variant | 4/6 | 1 | NM_178311.3 | P1 | |
GGTLC1 | ENST00000278765.8 | c.392C>T | p.Thr131Met | missense_variant | 4/6 | 1 | P1 | ||
GGTLC1 | ENST00000286890.8 | c.392C>T | p.Thr131Met | missense_variant | 3/5 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000215 AC: 54AN: 251110Hom.: 0 AF XY: 0.000251 AC XY: 34AN XY: 135718
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GnomAD4 exome AF: 0.000127 AC: 185AN: 1459710Hom.: 0 Cov.: 33 AF XY: 0.000117 AC XY: 85AN XY: 726162
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.392C>T (p.T131M) alteration is located in exon 4 (coding exon 3) of the GGTLC1 gene. This alteration results from a C to T substitution at nucleotide position 392, causing the threonine (T) at amino acid position 131 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
P;P;P
Vest4
MVP
MPC
0.62
ClinPred
D
GERP RS
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gMVP
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