Variant 7-135115461-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178563.4(AGBL3):c.2192A>C(p.Asp731Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000568 in 1,551,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

AGBL3
NM_178563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

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:

CYREN (HGNC:22432): (cell cycle regulator of NHEJ) Involved in double-strand break repair via nonhomologous end joining and negative regulation of double-strand break repair via nonhomologous end joining. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CYREN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12075704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL3	NM_178563.4 linkuse as main transcript	c.2192A>C	p.Asp731Ala	missense_variant	16/17	ENST00000436302.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL3	ENST00000436302.6 linkuse as main transcript	c.2192A>C	p.Asp731Ala	missense_variant	16/17	2	NM_178563.4	P2	Q8NEM8-4

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000593

AC:

830

AN:

1399080

Hom.:

Cov.:

AF XY:

0.000597

AC XY:

412

AN XY:

690056

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000751

Gnomad4 OTH exome

AF:

0.000259

GnomAD4 genome

AF:

0.000335

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000507

Hom.:

Bravo

AF:

0.000291

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2022

The c.2192A>C (p.D731A) alteration is located in exon 16 (coding exon 15) of the AGBL3 gene. This alteration results from a A to C substitution at nucleotide position 2192, causing the aspartic acid (D) at amino acid position 731 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.38

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.50

M_CAP

Benign

0.0081

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.080

REVEL

Benign

0.086

Sift

Uncertain

0.0020

Sift4G

Benign

0.56

Polyphen

1.0

Vest4

0.32

MVP

0.11

ClinPred

0.73

GERP RS

5.3

gMVP

0.20

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