rs371333741

Variant names:

• chr22-24611384-A-G
• rs371333741
• NM_001288833.2:c.164+139A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001288833.2(GGT1):​c.164+139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 659,482 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (709 hom., cov: 31)
  • Exomes 𝑓: 0.0088 (240 hom.)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 22-24611384-A-G is Benign according to our data. Variant chr22-24611384-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 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.164+139A>G		intron	N/A	NP_001275762.1	P19440-1
	GGT1	NM_013421.3		c.164+139A>G		intron	N/A	NP_038265.2	A0A140VJJ9
	GGT1	NM_013430.3		c.164+139A>G		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.164+139A>G		intron	N/A	ENSP00000383232.1	P19440-1
	GGT1	ENST00000400380.5	TSL:1	c.164+139A>G		intron	N/A	ENSP00000383231.1	P19440-1
	ENSG00000286070	ENST00000652248.1		n.*654+139A>G		intron	N/A	ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8187 AN: 152034 Hom.: 701 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0247

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0422

GnomAD4 exome AF: 0.00883 AC: 4478 AN: 507330 Hom.: 240 AF XY: 0.00856 AC XY: 2300 AN XY: 268684

African (AFR) AF: 0.174 AC: 2404 AN: 13800

American (AMR) AF: 0.0129 AC: 344 AN: 26650

Ashkenazi Jewish (ASJ) AF: 0.000514 AC: 8 AN: 15550

East Asian (EAS) AF: 0.000727 AC: 23 AN: 31636

South Asian (SAS) AF: 0.0190 AC: 964 AN: 50686

European-Finnish (FIN) AF: 0.000220 AC: 10 AN: 45490

Middle Eastern (MID) AF: 0.00894 AC: 19 AN: 2126

European-Non Finnish (NFE) AF: 0.000879 AC: 258 AN: 293490

Other (OTH) AF: 0.0161 AC: 448 AN: 27902

GnomAD4 genome AF: 0.0540 AC: 8219 AN: 152152 Hom.: 709 Cov.: 31 AF XY: 0.0524 AC XY: 3896 AN XY: 74406

African (AFR) AF: 0.182 AC: 7562 AN: 41470

American (AMR) AF: 0.0243 AC: 371 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5182

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4822

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 67994

Other (OTH) AF: 0.0413 AC: 87 AN: 2108

Alfa AF: 0.507 Hom.: 6682

Bravo AF: 0.0609

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0070
DANN	Benign	0.27
PhyloP100		-2.0
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: rs371333741; hg19: chr22-25007351;