20-34845413-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178026.3(GGT7):c.1904T>C(p.Val635Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GGT7 NM_178026.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGT7	NM_178026.3	c.1904T>C	p.Val635Ala	missense_variant	15/15	ENST00000336431.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGT7	ENST00000336431.10	c.1904T>C	p.Val635Ala	missense_variant	15/15	1	NM_178026.3	P1
GGT7	ENST00000469018.5	c.*210T>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jan 04, 2024

The c.1904T>C (p.V635A) alteration is located in exon 15 (coding exon 15) of the GGT7 gene. This alteration results from a T to C substitution at nucleotide position 1904, causing the valine (V) at amino acid position 635 to be replaced by an alanine (A). 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	0.55
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.70
MutPred		0.69		Loss of stability (P = 0.0089);
MVP		0.19
MPC		1.0
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.75
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs1371190273; hg19: chr20-33433216;