Variant rs12286721 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000525123.6(AGBL2):c.2013G>T(p.Met671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,587,002 control chromosomes in the GnomAD database, including 253,138 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.59 ( 27002 hom., cov: 29)

Exomes 𝑓: 0.56 ( 226136 hom. )

Consequence

AGBL2
ENST00000525123.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.506

Variant links:

Genes affected

AGBL2 (HGNC:26296): (AGBL carboxypeptidase 2) Predicted to enable metallocarboxypeptidase activity. Predicted to be involved in protein side chain deglutamylation. Located in centriole and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

AGBL2 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=2.6918674E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL2	NM_024783.4 linkuse as main transcript	c.2013G>T	p.Met671Ile	missense_variant	13/19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL2	ENST00000525123.6 linkuse as main transcript	c.2013G>T	p.Met671Ile	missense_variant	13/19	1	NM_024783.4	ENSP00000435582	P2	Q5U5Z8-1
AGBL2	ENST00000528609.5 linkuse as main transcript	c.*140G>T		3_prime_UTR_variant, NMD_transcript_variant	3/9	1		ENSP00000431912
AGBL2	ENST00000528244.5 linkuse as main transcript	c.1899G>T	p.Met633Ile	missense_variant	12/16	2		ENSP00000436630	A2
AGBL2	ENST00000529712.5 linkuse as main transcript	n.2547G>T		non_coding_transcript_exon_variant	10/11	2

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

89788

AN:

151222

Hom.:

26979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.744

Gnomad AMR

AF:

0.654

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.666

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.559

GnomAD3 exomes

AF:

0.581

AC:

144818

AN:

249432

Hom.:

43163

AF XY:

0.568

AC XY:

76574

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.738

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.547

Gnomad OTH exome

AF:

0.563

GnomAD4 exome

AF:

0.557

AC:

799242

AN:

1435662

Hom.:

226136

Cov.:

AF XY:

0.553

AC XY:

395936

AN XY:

715812

show subpopulations

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.727

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.676

Gnomad4 SAS exome

AF:

0.465

Gnomad4 FIN exome

AF:

0.647

Gnomad4 NFE exome

AF:

0.547

Gnomad4 OTH exome

AF:

0.553

GnomAD4 genome

AF:

0.594

AC:

89850

AN:

151340

Hom.:

27002

Cov.:

AF XY:

0.600

AC XY:

44315

AN XY:

73894

show subpopulations

Gnomad4 AFR

AF:

0.636

Gnomad4 AMR

AF:

0.654

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.614

Gnomad4 SAS

AF:

0.478

Gnomad4 FIN

AF:

0.666

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.563

Alfa

AF:

0.553

Hom.:

58748

Bravo

AF:

0.599

TwinsUK

AF:

0.551

AC:

2044

ALSPAC

AF:

0.556

AC:

2143

ESP6500AA

AF:

0.615

AC:

2709

ESP6500EA

AF:

0.546

AC:

4694

ExAC

AF:

0.572

AC:

69399

Asia WGS

AF:

0.511

AC:

1779

AN:

3478

EpiCase

AF:

0.543

EpiControl

AF:

0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0031

T;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.53

MetaRNN

Benign

0.0000027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.20

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.079

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.015

MutPred

0.19

Gain of methylation at K672 (P = 0.0258);Gain of methylation at K672 (P = 0.0258);.;

MPC

0.12

ClinPred

0.0046

GERP RS

0.55

Varity_R

0.082

gMVP

0.50

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