chr22-24611165-A-G

Position:

• chr22-24611165-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001288833.2(GGT1):​c.84A>G​(p.Ser28Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,552,864 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (114 hom., cov: 31)
  • Exomes 𝑓: 0.013 (221 hom.)
• Consequence: GGT1 NM_001288833.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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]

ENSG00000286070 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 22-24611165-A-G is Benign according to our data. Variant chr22-24611165-A-G is described in ClinVar as [Benign]. Clinvar id is 1248239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.84A>G	p.Ser28Ser	synonymous_variant	5/16	ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.84A>G	p.Ser28Ser	synonymous_variant	6/17		NP_038265.2
GGT1	NM_013430.3	c.84A>G	p.Ser28Ser	synonymous_variant	5/16		NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.84A>G	p.Ser28Ser	synonymous_variant	5/16	2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*574A>G		non_coding_transcript_exon_variant	9/20			ENSP00000499210.1
ENSG00000286070	ENST00000652248.1	n.*574A>G		3_prime_UTR_variant	9/20			ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4414 AN: 148264 Hom.: 111 Cov.: 31

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.0674

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0222

GnomAD3 exomes AF: 0.0139 AC: 2843 AN: 204198 Hom.: 47 AF XY: 0.0134 AC XY: 1489 AN XY: 111398

Gnomad AFR exome AF: 0.0511

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00293

Gnomad SAS exome AF: 0.0219

Gnomad FIN exome AF: 0.00718

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.0127 AC: 17810 AN: 1404486 Hom.: 221 Cov.: 31 AF XY: 0.0128 AC XY: 8936 AN XY: 698754

Gnomad4 AFR exome AF: 0.0576

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.000389

Gnomad4 EAS exome AF: 0.00284

Gnomad4 SAS exome AF: 0.0220

Gnomad4 FIN exome AF: 0.0115

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.0142

GnomAD4 genome AF: 0.0299 AC: 4442 AN: 148378 Hom.: 114 Cov.: 31 AF XY: 0.0294 AC XY: 2131 AN XY: 72464

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00158

Gnomad4 SAS AF: 0.0289

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0220

Alfa AF: 0.0218 Hom.: 16

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-1.0
CADD	Benign	0.55
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs4049897; hg19: chr22-25007132;