22-24225572-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004121.5(GGT5):c.1310G>A(p.Arg437Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,612,662 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 11 hom. )

Consequence

GGT5
NM_004121.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.484

Variant links:

Genes affected

GGT5 (HGNC:4260): (gamma-glutamyltransferase 5) This gene is a member of the gamma-glutamyl transpeptidase gene family, and some reports indicate that it is capable of cleaving the gamma-glutamyl moiety of glutathione. The protein encoded by this gene is synthesized as a single, catalytically-inactive polypeptide, that is processed post-transcriptionally to form a heavy and light subunit, with the catalytic activity contained within the small subunit. The encoded enzyme is able to convert leukotriene C4 to leukotriene D4, but appears to have distinct substrate specificity compared to gamma-glutamyl transpeptidase. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

GGT5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050580204).

BP6

Variant 22-24225572-C-T is Benign according to our data. Variant chr22-24225572-C-T is described in ClinVar as [Benign]. Clinvar id is 710165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00601 (915/152236) while in subpopulation AFR AF= 0.0211 (877/41546). AF 95% confidence interval is 0.02. There are 11 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGT5	NM_004121.5 link	c.1310G>A	p.Arg437Gln	missense_variant	Exon 9 of 12	ENST00000327365.10	NP_004112.2	P36269-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GGT5	ENST00000327365.10 link	c.1310G>A	p.Arg437Gln	missense_variant	Exon 9 of 12	1	NM_004121.5	ENSP00000330080.4	P36269-1
GGT5	ENST00000398292.3 link	c.1310G>A	p.Arg437Gln	missense_variant	Exon 9 of 12	1		ENSP00000381340.3	P36269-3
GGT5	ENST00000263112.11 link	c.1214G>A	p.Arg405Gln	missense_variant	Exon 8 of 11	1		ENSP00000263112.7	P36269-2
GGT5	ENST00000425408.5 link	c.116G>A	p.Arg39Gln	missense_variant	Exon 2 of 6	5		ENSP00000402917.1	H7C1X2

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

914

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00155

AC:

388

AN:

250810

Hom.:

AF XY:

0.00122

AC XY:

166

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000678

AC:

990

AN:

1460426

Hom.:

Cov.:

AF XY:

0.000637

AC XY:

463

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.0215

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00601

AC:

915

AN:

152236

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00680

ESP6500AA

AF:

0.0225

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00189

AC:

229

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.43

DANN

Benign

0.78

DEOGEN2

Benign

0.024

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0051

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

.;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.050

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.70

T;T;T

Sift4G

Benign

0.63

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.14

MVP

0.085

MPC

0.21

ClinPred

0.00070

GERP RS

-5.3

Varity_R

0.0080

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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