Variant rs11545078 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000260118.7(GGH):c.452C>T(p.Thr151Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0959 in 1,607,800 control chromosomes in the GnomAD database, including 8,203 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.079 ( 482 hom., cov: 33)

Exomes 𝑓: 0.098 ( 7721 hom. )

Consequence

GGH
ENST00000260118.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.18

Variant links:

Genes affected

GGH (HGNC:4248): (gamma-glutamyl hydrolase) This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate. [provided by RefSeq, Jul 2008]

GGH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017904639).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGH	NM_003878.3 linkuse as main transcript	c.452C>T	p.Thr151Ile	missense_variant	5/9	ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1 linkuse as main transcript	c.452C>T	p.Thr151Ile	missense_variant	5/8		NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7 linkuse as main transcript	c.452C>T	p.Thr151Ile	missense_variant	5/9	1	NM_003878.3	ENSP00000260118	P1

Frequencies

GnomAD3 genomes

AF:

0.0786

AC:

11963

AN:

152186

Hom.:

479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0529

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0538

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0747

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0589

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0947

Gnomad OTH

AF:

0.0785

GnomAD3 exomes

AF:

0.0878

AC:

21720

AN:

247448

Hom.:

1125

AF XY:

0.0949

AC XY:

12695

AN XY:

133760

show subpopulations

Gnomad AFR exome

AF:

0.0524

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.0769

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0557

Gnomad NFE exome

AF:

0.0943

Gnomad OTH exome

AF:

0.0897

GnomAD4 exome

AF:

0.0977

AC:

142159

AN:

1455496

Hom.:

7721

Cov.:

AF XY:

0.100

AC XY:

72708

AN XY:

724150

show subpopulations

Gnomad4 AFR exome

AF:

0.0504

Gnomad4 AMR exome

AF:

0.0386

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.0711

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.0985

Gnomad4 OTH exome

AF:

0.0948

GnomAD4 genome

AF:

0.0786

AC:

11976

AN:

152304

Hom.:

482

Cov.:

AF XY:

0.0784

AC XY:

5837

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0531

Gnomad4 AMR

AF:

0.0536

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0750

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0589

Gnomad4 NFE

AF:

0.0947

Gnomad4 OTH

AF:

0.0777

Alfa

AF:

0.0923

Hom.:

1451

Bravo

AF:

0.0765

TwinsUK

AF:

0.108

AC:

399

ALSPAC

AF:

0.101

AC:

390

ESP6500AA

AF:

0.0601

AC:

265

ESP6500EA

AF:

0.0960

AC:

826

ExAC

AF:

0.0935

AC:

11355

Asia WGS

AF:

0.117

AC:

413

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.0000017

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.19

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.028

Polyphen

0.63

Vest4

0.094

MPC

0.12

ClinPred

0.034

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.82

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over