rs3966262

Variant names:

• chr22-24610357-G-A
• rs3966262
• NM_001288833.2:c.-182G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001288833.2(GGT1):​c.-182G>A variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GGT1 NM_001288833.2 5_prime_UTR
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.-182G>A		5_prime_UTR_variant	Exon 4 of 16	ENST00000400382.6	NP_001275762.1
GGT1	NM_013430.3	c.-182G>A		5_prime_UTR_variant	Exon 4 of 16		NP_038347.2
GGT1	NM_013421.3	c.-181-1G>A		splice_acceptor_variant, intron_variant	Intron 4 of 16		NP_038265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.-182G>A		5_prime_UTR_variant	Exon 4 of 16	2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*310-1G>A		splice_acceptor_variant, intron_variant	Intron 7 of 19			ENSP00000499210.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	21
DANN	Benign	0.79
PhyloP100		2.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.75
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

Other links and lift over

dbSNP: rs3966262; hg19: chr22-25006324;