Variant 15-86247766-G-A 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.622G>A(p.Val208Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00985 in 1,613,968 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 15 hom., cov: 33)

Exomes 𝑓: 0.010 ( 95 hom. )

Consequence

AGBL1
NM_001386094.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.635

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=0.0034252703).

BP6

Variant 15-86247766-G-A is Benign according to our data. Variant chr15-86247766-G-A is described in ClinVar as [Benign]. Clinvar id is 2498623.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1030 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL1	NM_001386094.1 linkuse as main transcript	c.622G>A	p.Val208Met	missense_variant	7/23	ENST00000614907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL1	ENST00000614907.3 linkuse as main transcript	c.622G>A	p.Val208Met	missense_variant	7/23	5	NM_001386094.1	P4
AGBL1	ENST00000441037.7 linkuse as main transcript	c.622G>A	p.Val208Met	missense_variant	7/25	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00677

AC:

1030

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00611

AC:

1520

AN:

248680

Hom.:

AF XY:

0.00610

AC XY:

823

AN XY:

134984

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00448

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00646

GnomAD4 exome

AF:

0.0102

AC:

14864

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

7233

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.00532

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.00876

GnomAD4 genome

AF:

0.00676

AC:

1030

AN:

152334

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

466

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00954

Hom.:

Bravo

AF:

0.00667

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00278

AC:

ESP6500EA

AF:

0.0121

AC:

103

ExAC

AF:

0.00615

AC:

745

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

AGBL1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

Cadd

Benign

5.8

Dann

Benign

0.77

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.75

T;.

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

REVEL

Benign

0.046

Polyphen

0.67

.;P

MVP

0.067

MPC

0.011

ClinPred

0.0032

GERP RS

1.9

Varity_R

0.015

gMVP

0.13

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