rs2046975182

Variant names:

• chr22-24615070-G-A
• rs2046975182
• NM_001288833.2:c.325G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-24615070-G-A
• chr22-24615070-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001288833.2(GGT1):​c.325G>A​(p.Val109Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V109L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GGT1 NM_001288833.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

Genes affected

GGT1 (HGNC:4250): (gamma-glutamyltransferase 1) The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]

GGT1 Gene-Disease associations (from GenCC):

• gamma-glutamyl transpeptidase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ENSG00000286070 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30798775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288833.2. 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
	GGT1	NM_001288833.2	MANE Select	c.325G>A	p.Val109Met	missense	Exon 7 of 16	NP_001275762.1	P19440-1
	GGT1	NM_013421.3		c.325G>A	p.Val109Met	missense	Exon 8 of 17	NP_038265.2	A0A140VJJ9
	GGT1	NM_013430.3		c.325G>A	p.Val109Met	missense	Exon 7 of 16	NP_038347.2	P19440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGT1	ENST00000400382.6	TSL:2 MANE Select	c.325G>A	p.Val109Met	missense	Exon 7 of 16	ENSP00000383232.1	P19440-1
	GGT1	ENST00000400380.5	TSL:1	c.325G>A	p.Val109Met	missense	Exon 8 of 17	ENSP00000383231.1	P19440-1
	ENSG00000286070	ENST00000652248.1		n.*815G>A		non_coding_transcript_exon	Exon 11 of 20	ENSP00000499210.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.047
Sift	Benign	0.078	T
Sift4G	Uncertain	0.030	D
Polyphen		0.20	B
Vest4		0.27
MutPred		0.61		Gain of sheet (P = 0.1208)
MVP		0.16
ClinPred		0.50	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.65
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs2046975182; hg19: chr22-25011037;