22-24614614-CAAAAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chr22-24614614-C-CA
• rs4049879
• NM_001288833.2:c.165-145dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001288833.2(GGT1):​c.165-145dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 68,228 control chromosomes in the GnomAD database, including 99 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.051 (99 hom., cov: 29)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

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.165-145dupA		intron	N/A	NP_001275762.1	P19440-1
	GGT1	NM_013421.3		c.165-145dupA		intron	N/A	NP_038265.2	A0A140VJJ9
	GGT1	NM_013430.3		c.165-145dupA		intron	N/A	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.165-162_165-161insA		intron	N/A	ENSP00000383232.1	P19440-1
	GGT1	ENST00000400380.5	TSL:1	c.165-162_165-161insA		intron	N/A	ENSP00000383231.1	P19440-1
	ENSG00000286070	ENST00000652248.1		n.*655-162_*655-161insA		intron	N/A	ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 3444 AN: 68212 Hom.: 100 Cov.: 29

Gnomad AFR AF: 0.0986

Gnomad AMI AF: 0.0383

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00439

Gnomad SAS AF: 0.0123

Gnomad FIN AF: 0.00994

Gnomad MID AF: 0.0244

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0379

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0506 AC: 3451 AN: 68228 Hom.: 99 Cov.: 29 AF XY: 0.0496 AC XY: 1587 AN XY: 31982

African (AFR) AF: 0.0987 AC: 2384 AN: 24142

American (AMR) AF: 0.0328 AC: 191 AN: 5818

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 71 AN: 1710

East Asian (EAS) AF: 0.00441 AC: 9 AN: 2040

South Asian (SAS) AF: 0.0124 AC: 23 AN: 1852

European-Finnish (FIN) AF: 0.00994 AC: 24 AN: 2414

Middle Eastern (MID) AF: 0.0250 AC: 2 AN: 80

European-Non Finnish (NFE) AF: 0.0241 AC: 698 AN: 28904

Other (OTH) AF: 0.0388 AC: 35 AN: 902

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	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: rs4049879; hg19: chr22-25010581;