Variant 7-134993576-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_178563.4(AGBL3):c.208C>T(p.Arg70Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,551,844 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 73 hom. )

Consequence

AGBL3
NM_178563.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.03

Variant links:

Genes affected

AGBL3 (HGNC:27981): (AGBL carboxypeptidase 3) Enables metallocarboxypeptidase activity. Involved in protein side chain deglutamylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

AGBL3 links:

(HGNC:):

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=0.010233521).

BP6

Variant 7-134993576-C-T is Benign according to our data. Variant chr7-134993576-C-T is described in ClinVar as [Benign]. Clinvar id is 783007.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL3	NM_178563.4 linkuse as main transcript	c.208C>T	p.Arg70Cys	missense_variant	4/17	ENST00000436302.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL3	ENST00000436302.6 linkuse as main transcript	c.208C>T	p.Arg70Cys	missense_variant	4/17	2	NM_178563.4	P2	Q8NEM8-4
	ENST00000665703.1 linkuse as main transcript	n.71+4507G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00623

AC:

948

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00774

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00533

AC:

842

AN:

158014

Hom.:

AF XY:

0.00532

AC XY:

444

AN XY:

83418

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.000971

Gnomad ASJ exome

AF:

0.000234

Gnomad EAS exome

AF:

0.000275

Gnomad SAS exome

AF:

0.000966

Gnomad FIN exome

AF:

0.00768

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00291

GnomAD4 exome

AF:

0.00880

AC:

12323

AN:

1399612

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

5896

AN XY:

690292

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.000238

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.00757

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00585

GnomAD4 genome

AF:

0.00623

AC:

948

AN:

152232

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

443

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00774

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00917

Hom.:

Bravo

AF:

0.00544

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00880

AC:

ExAC

AF:

0.00410

AC:

105

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.010

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.66

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.50

MVP

0.36

ClinPred

0.036

GERP RS

4.9

gMVP

0.62

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