20-34851277-G-C

Variant summary

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

The NM_178026.3(GGT7):c.1679C>G(p.Ala560Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A560T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GGT7 NM_178026.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGT7	NM_178026.3	c.1679C>G	p.Ala560Gly	missense_variant	13/15	ENST00000336431.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGT7	ENST00000336431.10	c.1679C>G	p.Ala560Gly	missense_variant	13/15	1	NM_178026.3	P1
GGT7	ENST00000470952.2	c.212C>G	p.Ala71Gly	missense_variant	2/3	5
GGT7	ENST00000469018.5	c.305C>G	p.Ala102Gly	missense_variant, NMD_transcript_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.1679C>G (p.A560G) alteration is located in exon 13 (coding exon 13) of the GGT7 gene. This alteration results from a C to G substitution at nucleotide position 1679, causing the alanine (A) at amino acid position 560 to be replaced by a glycine (G). 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	0.18
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.24
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.096	T
Polyphen		0.77	P
Vest4		0.68
MutPred		0.72		Loss of stability (P = 0.0613);
MVP		0.18
MPC		0.49
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.30
gMVP		0.86

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: chr20-33439080;