dbSNP rs772658673: GGT7:p.Arg520Pro (chr20-34852183-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_178026.3(GGT7):c.1559G>C(p.Arg520Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R520Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GGT7
NM_178026.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

Publications

0 publications found

Variant links:

Genes affected

GGT7 (HGNC:4259): (gamma-glutamyltransferase 7) This gene is a member of a gene family that encodes enzymes involved in both the metabolism of glutathione and in the transpeptidation of amino acids. Changes in the activity of gamma-glutamyltransferase may signal preneoplastic or toxic conditions in the liver or kidney. The protein encoded by this gene consists of a heavy and a light chain, and it can interact with CT120, a plasma membrane-associated protein that is possibly involved in lung carcinogenesis. [provided by RefSeq, Jul 2008]

GGT7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29719275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178026.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGT7	NM_178026.3	MANE Select	c.1559G>C	p.Arg520Pro	missense	Exon 12 of 15	NP_821158.2	Q9UJ14-1
	GGT7	NM_001351702.2		c.1559G>C	p.Arg520Pro	missense	Exon 12 of 15	NP_001338631.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGT7	ENST00000336431.10	TSL:1 MANE Select	c.1559G>C	p.Arg520Pro	missense	Exon 12 of 15	ENSP00000338964.5	Q9UJ14-1
GGT7	ENST00000885994.1		c.1598G>C	p.Arg533Pro	missense	Exon 12 of 15	ENSP00000556053.1
GGT7	ENST00000885991.1		c.1571G>C	p.Arg524Pro	missense	Exon 12 of 15	ENSP00000556050.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251326

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460566

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726674

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110842

Other (OTH)

AF:

0.00

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0059

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

3.2

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Benign

0.12

Sift4G

Uncertain

0.012

Polyphen

0.74

Vest4

0.50

MutPred

0.50

Gain of catalytic residue at R520 (P = 0.0048)

MVP

0.068

MPC

0.59

ClinPred

0.62

GERP RS

5.0

PromoterAI

-0.0018

Neutral

(source)

Varity_R

0.27

gMVP

0.88

Mutation Taster

=38/62

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over