22-24595896-C-T

Variant names:

• chr22-24595896-C-T
• rs6519519
• ENST00000652248.1:n.*168-12058C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013430.3(GGT1):​c.-428-12058C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,174 control chromosomes in the GnomAD database, including 8,050 homozygotes. 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: 𝑓 0.32 (8050 hom., cov: 33)
• Consequence: GGT1 NM_013430.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 10 publications found

Genes affected

ENSG00000286070 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013430.3. 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_013430.3		c.-428-12058C>T		intron	N/A	NP_038347.2	P19440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286070	ENST00000652248.1		n.*168-12058C>T		intron	N/A	ENSP00000499210.1
	GGT1	ENST00000875906.1		c.-429+1010C>T		intron	N/A	ENSP00000545965.1
	GGT1	ENST00000875907.1		c.-252+1010C>T		intron	N/A	ENSP00000545966.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48311 AN: 152056 Hom.: 8042 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.318 AC: 48357 AN: 152174 Hom.: 8050 Cov.: 33 AF XY: 0.313 AC XY: 23249 AN XY: 74396

African (AFR) AF: 0.402 AC: 16690 AN: 41512

American (AMR) AF: 0.391 AC: 5974 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1199 AN: 5180

South Asian (SAS) AF: 0.241 AC: 1162 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2317 AN: 10592

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19023 AN: 68006

Other (OTH) AF: 0.331 AC: 699 AN: 2112

Alfa AF: 0.290 Hom.: 4793

Bravo AF: 0.338

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.59
PhyloP100		0.17
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: rs6519519; hg19: chr22-24991863; COSMIC: COSV50646223; COSMIC: COSV50646223;