20-34872724-G-C

Variant names:

• chr20-34872724-G-C
• NM_178026.3:c.92C>G

Variant summary

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

The NM_178026.3(GGT7):​c.92C>G​(p.Pro31Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GGT7 NM_178026.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

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]

ACSS2 (HGNC:15814): (acyl-CoA synthetase short chain family member 2) This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

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 rank	MANE	Protein	UniProt
GGT7	NM_178026.3	c.92C>G	p.Pro31Arg	missense_variant	Exon 1 of 15	ENST00000336431.10	NP_821158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGT7	ENST00000336431.10	c.92C>G	p.Pro31Arg	missense_variant	Exon 1 of 15	1	NM_178026.3	ENSP00000338964.5
GGT7	ENST00000427420.1	c.92C>G	p.Pro31Arg	missense_variant	Exon 1 of 4	2		ENSP00000394993.1
ACSS2	ENST00000490046.1	n.258+321G>C		intron_variant	Intron 1 of 1	4
ACSS2	ENST00000481971.5	n.-158G>C		upstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.92C>G (p.P31R) alteration is located in exon 1 (coding exon 1) of the GGT7 gene. This alteration results from a C to G substitution at nucleotide position 92, causing the proline (P) at amino acid position 31 to be replaced by an arginine (R). 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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.12	T;.
Polyphen		1.0	D;.
Vest4		0.70
MutPred		0.31		Loss of glycosylation at P31 (P = 0.0554);Loss of glycosylation at P31 (P = 0.0554);
MVP		0.18
MPC		2.2
ClinPred		0.98	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr20-33460527;