NM_178026.3:c.1454T>C

Variant names:

• chr20-34852404-A-G
• rs1477926349
• NM_178026.3:c.1454T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_178026.3(GGT7):​c.1454T>C​(p.Ile485Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GGT7 NM_178026.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.66
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.1454T>C	p.Ile485Thr	missense	Exon 11 of 15	NP_821158.2	Q9UJ14-1
	GGT7	NM_001351702.2		c.1454T>C	p.Ile485Thr	missense	Exon 11 of 15	NP_001338631.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGT7	ENST00000336431.10	TSL:1 MANE Select	c.1454T>C	p.Ile485Thr	missense	Exon 11 of 15	ENSP00000338964.5	Q9UJ14-1
	GGT7	ENST00000885994.1		c.1493T>C	p.Ile498Thr	missense	Exon 11 of 15	ENSP00000556053.1
	GGT7	ENST00000885991.1		c.1466T>C	p.Ile489Thr	missense	Exon 11 of 15	ENSP00000556050.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461838 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.7
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.64		Loss of stability (P = 0.0535)
MVP		0.14
MPC		1.1
ClinPred		0.88	D
GERP RS		6.2
PromoterAI		-0.015	Neutral
Varity_R		0.42
gMVP		0.87
Mutation Taster		=32/68	disease causing

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

Other links and lift over

dbSNP: rs1477926349; hg19: chr20-33440207;