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22-24620344-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001288833.2(GGT1):c.399G>A(p.Ala133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,611,592 control chromosomes in the GnomAD database, including 526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.033 ( 280 hom., cov: 32)
Exomes 𝑓: 0.0057 ( 246 hom. )

Consequence

GGT1
NM_001288833.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.49
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-24620344-G-A is Benign according to our data. Variant chr22-24620344-G-A is described in ClinVar as [Benign]. Clinvar id is 1252200.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.49 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GGT1NM_001288833.2 linkuse as main transcriptc.399G>A p.Ala133= synonymous_variant 8/16 ENST00000400382.6
GGT1NM_013421.3 linkuse as main transcriptc.399G>A p.Ala133= synonymous_variant 9/17
GGT1NM_013430.3 linkuse as main transcriptc.399G>A p.Ala133= synonymous_variant 8/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GGT1ENST00000400382.6 linkuse as main transcriptc.399G>A p.Ala133= synonymous_variant 8/162 NM_001288833.2 P1P19440-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0333
AC:
5063
AN:
152112
Hom.:
277
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.109
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0190
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00237
Gnomad OTH
AF:
0.0301
GnomAD3 exomes
AF:
0.00928
AC:
2276
AN:
245374
Hom.:
68
AF XY:
0.00758
AC XY:
1015
AN XY:
133850
show subpopulations
Gnomad AFR exome
AF:
0.109
Gnomad AMR exome
AF:
0.00835
Gnomad ASJ exome
AF:
0.000502
Gnomad EAS exome
AF:
0.0000558
Gnomad SAS exome
AF:
0.00141
Gnomad FIN exome
AF:
0.000374
Gnomad NFE exome
AF:
0.00288
Gnomad OTH exome
AF:
0.00604
GnomAD4 exome
AF:
0.00570
AC:
8323
AN:
1459362
Hom.:
246
Cov.:
33
AF XY:
0.00524
AC XY:
3805
AN XY:
725998
show subpopulations
Gnomad4 AFR exome
AF:
0.113
Gnomad4 AMR exome
AF:
0.0105
Gnomad4 ASJ exome
AF:
0.000574
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00139
Gnomad4 FIN exome
AF:
0.000506
Gnomad4 NFE exome
AF:
0.00297
Gnomad4 OTH exome
AF:
0.00989
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0334
AC:
5077
AN:
152230
Hom.:
280
Cov.:
32
AF XY:
0.0318
AC XY:
2369
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.109
Gnomad4 AMR
AF:
0.0190
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00237
Gnomad4 OTH
AF:
0.0293
Alfa
AF:
0.00857
Hom.:
12
Bravo
AF:
0.0383
EpiCase
AF:
0.00284
EpiControl
AF:
0.00326

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 submitterclinical testingGeneDxJun 15, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
0.064
Dann
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs183458338; hg19: chr22-25016311; COSMIC: COSV50645339; COSMIC: COSV50645339; API