Genetic Variant GGCT:p.Arg108Leu (chr7-30497200-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 14/17 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 Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GGCT
NM_001199815.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.421

Publications

0 publications found

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]

GGCT links:

ENSG00000281039 (HGNC:):

ENSG00000281039 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040880322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199815.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGCT	NM_024051.4	MANE Select	c.459G>T	p.Pro153Pro	synonymous	Exon 4 of 4	NP_076956.1	O75223-1
GGCT	NM_001199815.2		c.479G>T	p.Arg160Leu	missense	Exon 4 of 4	NP_001186744.1	O75223-4
GGCT	NM_001199816.2		c.323G>T	p.Arg108Leu	missense	Exon 3 of 3	NP_001186745.1	O75223-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGCT	ENST00000005374.10	TSL:1	c.323G>T	p.Arg108Leu	missense	Exon 3 of 3	ENSP00000005374.6	O75223-2
GGCT	ENST00000275428.9	TSL:1 MANE Select	c.459G>T	p.Pro153Pro	synonymous	Exon 4 of 4	ENSP00000275428.4	O75223-1
ENSG00000281039	ENST00000598361.4	TSL:5	c.204G>T	p.Pro68Pro	synonymous	Exon 5 of 5	ENSP00000470615.1	M0QZK8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458582

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725662

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

44302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39588

South Asian (SAS)

AF:

0.00

AC:

AN:

85714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110368

Other (OTH)

AF:

0.0000166

AC:

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.49

(source)

DANN

Benign

0.96

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.33

M_CAP

Benign

0.0057

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

PhyloP100

-0.42

PROVEAN

Benign

-0.42

REVEL

Benign

0.23

Sift

Benign

0.074

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.060

MutPred

0.49

Loss of disorder (P = 0.0383)

MVP

0.27

ClinPred

0.15

GERP RS

-12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over