Variant 22-24620344-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001288833.2(GGT1):c.399G>A(p.Ala133Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,611,592 control chromosomes in the GnomAD database, including 526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 280 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 246 hom. )

Consequence

GGT1
NM_001288833.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.49

Variant links:

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 links:

ENSG00000286070 (HGNC:):

ENSG00000286070 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 22-24620344-G-A is Benign according to our data. Variant chr22-24620344-G-A is described in ClinVar as [Benign]. Clinvar id is 1252200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2 linkuse as main transcript	c.399G>A	p.Ala133Ala	synonymous_variant	8/16	ENST00000400382.6	NP_001275762.1	P19440-1A0A140VJJ9
GGT1	NM_013421.3 linkuse as main transcript	c.399G>A	p.Ala133Ala	synonymous_variant	9/17		NP_038265.2	P19440-1A0A140VJJ9
GGT1	NM_013430.3 linkuse as main transcript	c.399G>A	p.Ala133Ala	synonymous_variant	8/16		NP_038347.2	P19440-1A0A140VJJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GGT1	ENST00000400382.6 linkuse as main transcript	c.399G>A	p.Ala133Ala	synonymous_variant	8/16	2	NM_001288833.2	ENSP00000383232.1	P19440-1
ENSG00000286070	ENST00000652248.1 linkuse as main transcript	n.*889G>A		non_coding_transcript_exon_variant	12/20			ENSP00000499210.1
ENSG00000286070	ENST00000652248.1 linkuse as main transcript	n.*889G>A		3_prime_UTR_variant	12/20			ENSP00000499210.1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5063

AN:

152112

Hom.:

277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.00928

AC:

2276

AN:

245374

Hom.:

AF XY:

0.00758

AC XY:

1015

AN XY:

133850

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.00835

Gnomad ASJ exome

AF:

0.000502

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.000374

Gnomad NFE exome

AF:

0.00288

Gnomad OTH exome

AF:

0.00604

GnomAD4 exome

AF:

0.00570

AC:

8323

AN:

1459362

Hom.:

246

Cov.:

AF XY:

0.00524

AC XY:

3805

AN XY:

725998

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.00297

Gnomad4 OTH exome

AF:

0.00989

GnomAD4 genome

AF:

0.0334

AC:

5077

AN:

152230

Hom.:

280

Cov.:

AF XY:

0.0318

AC XY:

2369

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.00857

Hom.:

Bravo

AF:

0.0383

EpiCase

AF:

0.00284

EpiControl

AF:

0.00326

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.064

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over