rs4049844
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001288833.2(GGT1):c.384G>A(p.Gly128Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
GGT1
NM_001288833.2 splice_region, synonymous
NM_001288833.2 splice_region, synonymous
Scores
3
Splicing: ADA: 0.00001150
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.798
Publications
7 publications found
Genes affected
GGT1 (HGNC:4250): (gamma-glutamyltransferase 1) The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]
GGT1 Gene-Disease associations (from GenCC):
- gamma-glutamyl transpeptidase deficiencyInheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_001288833.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP7
Synonymous conserved (PhyloP=-0.798 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001288833.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GGT1 | MANE Select | c.384G>A | p.Gly128Gly | splice_region synonymous | Exon 8 of 16 | NP_001275762.1 | P19440-1 | ||
| GGT1 | c.384G>A | p.Gly128Gly | splice_region synonymous | Exon 9 of 17 | NP_038265.2 | A0A140VJJ9 | |||
| GGT1 | c.384G>A | p.Gly128Gly | splice_region synonymous | Exon 8 of 16 | NP_038347.2 | P19440-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GGT1 | TSL:2 MANE Select | c.384G>A | p.Gly128Gly | splice_region synonymous | Exon 8 of 16 | ENSP00000383232.1 | P19440-1 | ||
| GGT1 | TSL:1 | c.384G>A | p.Gly128Gly | splice_region synonymous | Exon 9 of 17 | ENSP00000383231.1 | P19440-1 | ||
| ENSG00000286070 | n.*874G>A | splice_region non_coding_transcript_exon | Exon 12 of 20 | ENSP00000499210.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00219 AC: 465AN: 211860 AF XY: 0.00149 show subpopulations
GnomAD2 exomes
AF:
AC:
465
AN:
211860
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459410Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726028 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1459410
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
726028
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33404
American (AMR)
AF:
AC:
0
AN:
44672
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26106
East Asian (EAS)
AF:
AC:
0
AN:
39692
South Asian (SAS)
AF:
AC:
0
AN:
86134
European-Finnish (FIN)
AF:
AC:
0
AN:
53338
Middle Eastern (MID)
AF:
AC:
0
AN:
4136
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111742
Other (OTH)
AF:
AC:
0
AN:
60186
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00250614), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
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60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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