7-30504583-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024051.4(GGCT):​c.127G>A​(p.Val43Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,370 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: not found (cov: 34)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GGCT
NM_024051.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34
Variant links:
Genes affected
GGCT (HGNC:21705): (gamma-glutamylcyclotransferase) The protein encoded by this gene catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides, the penultimate step in glutathione catabolism, and may play a critical role in glutathione homeostasis. The encoded protein may also play a role in cell proliferation, and the expression of this gene is a potential marker for cancer. Pseudogenes of this gene are located on the long arm of chromosome 5 and the short arm of chromosomes 2 and 20. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33554006).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGCTNM_024051.4 linkc.127G>A p.Val43Met missense_variant Exon 1 of 4 ENST00000275428.9 NP_076956.1 O75223-1A0A090N7V5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GGCTENST00000275428.9 linkc.127G>A p.Val43Met missense_variant Exon 1 of 4 1 NM_024051.4 ENSP00000275428.4 O75223-1
ENSG00000281039ENST00000598361.4 linkc.-114-3902G>A intron_variant Intron 2 of 4 5 ENSP00000470615.1 M0QZK8

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250050
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135312
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461370
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.127G>A (p.V43M) alteration is located in exon 1 (coding exon 1) of the GGCT gene. This alteration results from a G to A substitution at nucleotide position 127, causing the valine (V) at amino acid position 43 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Uncertain
0.086
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.089
T;.;.;.;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
D;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.34
T;T;T;T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Pathogenic
3.1
M;M;M;M;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.4
N;N;N;N;N
REVEL
Benign
0.23
Sift
Uncertain
0.013
D;T;D;T;D
Sift4G
Uncertain
0.059
T;D;D;T;D
Polyphen
1.0
D;D;.;.;.
Vest4
0.47
MutPred
0.49
Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);
MVP
0.74
MPC
0.94
ClinPred
0.94
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1234239760; hg19: chr7-30544199; API