rs115910467

Variant names:

• chr7-30497200-C-A
• ENST00000005374.10:c.323G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-30497200-C-A
• chr7-30497200-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199815.2(GGCT):​c.479G>T​(p.Arg160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R160H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GGCT NM_001199815.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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]

ENSG00000281039 (HGNC:):

ACMG classification

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=0.040880322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGCT	NM_024051.4	c.459G>T	p.Pro153Pro	synonymous_variant	Exon 4 of 4	ENST00000275428.9	NP_076956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGCT	ENST00000275428.9	c.459G>T	p.Pro153Pro	synonymous_variant	Exon 4 of 4	1	NM_024051.4	ENSP00000275428.4
ENSG00000281039	ENST00000598361.4	c.204G>T	p.Pro68Pro	synonymous_variant	Exon 5 of 5	5		ENSP00000470615.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458582 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725662

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.49
DANN	Benign	0.96
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.23
Sift	Benign	0.074	T;T
Sift4G	Benign	0.12	T;D
Polyphen		0.0	B;.
Vest4		0.060
MutPred		0.49		Loss of disorder (P = 0.0383);.;
MVP		0.27
ClinPred		0.15	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr7-30536816;