NM_001288833.2:c.165-145delA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001288833.2(GGT1):​c.165-145delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 68,550 control chromosomes in the GnomAD database, including 500 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (500 hom., cov: 29)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 22-24614614-CA-C is Benign according to our data. Variant chr22-24614614-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1294465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 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.165-145delA		intron	N/A	NP_001275762.1	P19440-1
	GGT1	NM_013421.3		c.165-145delA		intron	N/A	NP_038265.2	A0A140VJJ9
	GGT1	NM_013430.3		c.165-145delA		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.165-161delA		intron	N/A	ENSP00000383232.1	P19440-1
	GGT1	ENST00000400380.5	TSL:1	c.165-161delA		intron	N/A	ENSP00000383231.1	P19440-1
	ENSG00000286070	ENST00000652248.1		n.*655-161delA		intron	N/A	ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 7482 AN: 68534 Hom.: 499 Cov.: 29

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.0310

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.00413

Gnomad MID AF: 0.0610

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.109 AC: 7493 AN: 68550 Hom.: 500 Cov.: 29 AF XY: 0.109 AC XY: 3489 AN XY: 32136

African (AFR) AF: 0.264 AC: 6389 AN: 24162

American (AMR) AF: 0.0745 AC: 435 AN: 5840

Ashkenazi Jewish (ASJ) AF: 0.0310 AC: 53 AN: 1712

East Asian (EAS) AF: 0.0190 AC: 39 AN: 2052

South Asian (SAS) AF: 0.0605 AC: 112 AN: 1852

European-Finnish (FIN) AF: 0.00413 AC: 10 AN: 2420

Middle Eastern (MID) AF: 0.0625 AC: 5 AN: 80

European-Non Finnish (NFE) AF: 0.0125 AC: 363 AN: 29154

Other (OTH) AF: 0.0956 AC: 87 AN: 910

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV104373965; COSMIC: COSV104373965;