chr22-24615353-T-C

Variant names:

• chr22-24615353-T-C
• rs28377326
• NM_001288833.2:c.382+226T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001288833.2(GGT1):​c.382+226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,810 control chromosomes in the GnomAD database, including 18,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (18808 hom., cov: 31)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.21
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 22-24615353-T-C is Benign according to our data. Variant chr22-24615353-T-C is described in ClinVar as Benign. ClinVar VariationId is 1236112.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 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.382+226T>C		intron	N/A	NP_001275762.1	P19440-1
	GGT1	NM_013421.3		c.382+226T>C		intron	N/A	NP_038265.2	A0A140VJJ9
	GGT1	NM_013430.3		c.382+226T>C		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.382+226T>C		intron	N/A	ENSP00000383232.1	P19440-1
	GGT1	ENST00000400380.5	TSL:1	c.382+226T>C		intron	N/A	ENSP00000383231.1	P19440-1
	ENSG00000286070	ENST00000652248.1		n.*872+226T>C		intron	N/A	ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69450 AN: 151686 Hom.: 18762 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.458 AC: 69559 AN: 151810 Hom.: 18808 Cov.: 31 AF XY: 0.452 AC XY: 33574 AN XY: 74220

African (AFR) AF: 0.762 AC: 31526 AN: 41352

American (AMR) AF: 0.459 AC: 7000 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1475 AN: 3464

East Asian (EAS) AF: 0.337 AC: 1736 AN: 5144

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3151 AN: 10580

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 22017 AN: 67874

Other (OTH) AF: 0.444 AC: 937 AN: 2110

Alfa AF: 0.153 Hom.: 250

Bravo AF: 0.487

Asia WGS AF: 0.348 AC: 1207 AN: 3478

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.079
DANN	Benign	0.65
PhyloP100		-2.2
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: rs28377326; hg19: chr22-25011320;