Variant 15-86256923-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001386094.1(AGBL1):c.806C>T(p.Pro269Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0117 in 1,613,926 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 5 hom., cov: 32)

Exomes 𝑓: 0.012 ( 121 hom. )

Consequence

AGBL1
NM_001386094.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.27

Variant links:

Genes affected

AGBL1 (HGNC:26504): (AGBL carboxypeptidase 1) Polyglutamylation is a reversible posttranslational modification catalyzed by polyglutamylases that results in the addition of glutamate side chains on the modified protein. This gene encodes a glutamate decarboxylase that catalyzes the deglutamylation of polyglutamylated proteins. Mutations in this gene result in dominant late-onset Fuchs corneal dystrophy. [provided by RefSeq, Nov 2013]

AGBL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005311519).

BP6

Variant 15-86256923-C-T is Benign according to our data. Variant chr15-86256923-C-T is described in ClinVar as [Benign]. Clinvar id is 3059001.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	8/23	ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	8/23	5	NM_001386094.1	P4
AGBL1	ENST00000441037.7 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	8/25	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00896

AC:

1364

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00816

AC:

2031

AN:

248996

Hom.:

AF XY:

0.00784

AC XY:

1059

AN XY:

135076

show subpopulations

Gnomad AFR exome

AF:

0.00465

Gnomad AMR exome

AF:

0.00604

Gnomad ASJ exome

AF:

0.00497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.00395

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.00777

GnomAD4 exome

AF:

0.0120

AC:

17571

AN:

1461610

Hom.:

121

Cov.:

AF XY:

0.0116

AC XY:

8454

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00394

Gnomad4 AMR exome

AF:

0.00653

Gnomad4 ASJ exome

AF:

0.00448

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.00466

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.00896

AC:

1365

AN:

152316

Hom.:

Cov.:

AF XY:

0.00846

AC XY:

630

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00983

TwinsUK

AF:

0.0124

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00385

AC:

ESP6500EA

AF:

0.0133

AC:

112

ExAC

AF:

0.00820

AC:

992

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0137

EpiControl

AF:

0.0142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AGBL1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;.

MetaRNN

Benign

0.0053

T;T

MetaSVM

Uncertain

-0.13

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

REVEL

Uncertain

0.31

Polyphen

1.0

.;D

MVP

0.72

MPC

0.064

ClinPred

0.030

GERP RS

5.9

Varity_R

0.13

gMVP

0.45

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