7-30500537-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_024051.4(GGCT):​c.286G>A​(p.Glu96Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GGCT
NM_024051.4 missense, splice_region

Scores

1
17
Splicing: ADA: 0.0009003
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.210
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 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=0.09024668).
BP6
Variant 7-30500537-C-T is Benign according to our data. Variant chr7-30500537-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3519976.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGCTNM_024051.4 linkc.286G>A p.Glu96Lys missense_variant, splice_region_variant Exon 2 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.286G>A p.Glu96Lys missense_variant, splice_region_variant Exon 2 of 4 1 NM_024051.4 ENSP00000275428.4 O75223-1
ENSG00000281039ENST00000598361.4 linkc.31G>A p.Glu11Lys missense_variant, splice_region_variant Exon 3 of 5 5 ENSP00000470615.1 M0QZK8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458584
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725776
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 30, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
14
DANN
Benign
0.54
DEOGEN2
Benign
0.036
T;.;.;T;.
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.27
N
LIST_S2
Uncertain
0.90
D;T;T;D;D
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.090
T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.71
N;N;N;N;.
REVEL
Benign
0.19
Sift
Benign
1.0
T;T;T;T;.
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;B;.;.;.
Vest4
0.11
MutPred
0.40
Gain of ubiquitination at E96 (P = 0.0128);Gain of ubiquitination at E96 (P = 0.0128);Gain of ubiquitination at E96 (P = 0.0128);Gain of ubiquitination at E96 (P = 0.0128);.;
MVP
0.32
MPC
0.38
ClinPred
0.46
T
GERP RS
1.1
Varity_R
0.12
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00090
dbscSNV1_RF
Benign
0.19
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: chr7-30540153; API