7-30500656-G-C

Variant names:

• chr7-30500656-G-C
• ENST00000598361.4:c.-89C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000598361.4(ENSG00000281039):​c.-89C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENSG00000281039 ENST00000598361.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.338

Genes affected

ENSG00000281039 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11606428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGCT	NM_024051.4	c.167C>G	p.Ser56Cys	missense_variant	Exon 2 of 4	ENST00000275428.9	NP_076956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000281039	ENST00000598361.4	c.-89C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 5	5		ENSP00000470615.1
GGCT	ENST00000275428.9	c.167C>G	p.Ser56Cys	missense_variant	Exon 2 of 4	1	NM_024051.4	ENSP00000275428.4
ENSG00000281039	ENST00000598361.4	c.-89C>G		5_prime_UTR_variant	Exon 3 of 5	5		ENSP00000470615.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167C>G (p.S56C) alteration is located in exon 2 (coding exon 2) of the GGCT gene. This alteration results from a C to G substitution at nucleotide position 167, causing the serine (S) at amino acid position 56 to be replaced by a cysteine (C). 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	0.077
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.072	T;.;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L;L;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.20
MutPred		0.42		Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);Loss of disorder (P = 0);
MVP		0.45
MPC		0.33
ClinPred		0.096	T
GERP RS		-1.3
Varity_R		0.11
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-30540272;