20-34851271-C-G

Variant names:

• chr20-34851271-C-G
• rs371319730
• NM_178026.3:c.1685G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_178026.3(GGT7):​c.1685G>C​(p.Gly562Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: GGT7 NM_178026.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80

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 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.963
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGT7	NM_178026.3	c.1685G>C	p.Gly562Ala	missense_variant	Exon 13 of 15	ENST00000336431.10	NP_821158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGT7	ENST00000336431.10	c.1685G>C	p.Gly562Ala	missense_variant	Exon 13 of 15	1	NM_178026.3	ENSP00000338964.5
GGT7	ENST00000470952.2	c.215G>C	p.Gly72Ala	missense_variant	Exon 2 of 3	5		ENSP00000486190.1
GGT7	ENST00000469018.5	n.308G>C		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000486589.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461538 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727078

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1685G>C (p.G562A) alteration is located in exon 13 (coding exon 13) of the GGT7 gene. This alteration results from a G to C substitution at nucleotide position 1685, causing the glycine (G) at amino acid position 562 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	Benign	0.13
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.68
Sift	Benign	0.079	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.89		Loss of sheet (P = 0.0357);
MVP		0.62
MPC		0.51
ClinPred		1.0	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs371319730; hg19: chr20-33439074;