Variant 7-135034546-C-T 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.955C>T(p.Arg319Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000464 in 1,551,870 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

AGBL3
NM_178563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.586

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:

Genome browser will be placed here

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=0.13612443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL3	NM_178563.4 linkuse as main transcript	c.955C>T	p.Arg319Trp	missense_variant	7/17	ENST00000436302.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL3	ENST00000436302.6 linkuse as main transcript	c.955C>T	p.Arg319Trp	missense_variant	7/17	2	NM_178563.4	P2	Q8NEM8-4
AGBL3	ENST00000275763.10 linkuse as main transcript	c.955C>T	p.Arg319Trp	missense_variant, NMD_transcript_variant	7/17	1			Q8NEM8-2
AGBL3	ENST00000435976.6 linkuse as main transcript	c.955C>T	p.Arg319Trp	missense_variant	7/16	5		A2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000761

AC:

AN:

157774

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

83318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000367

Gnomad SAS exome

AF:

0.000220

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1399600

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

690306

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000196

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000371

Gnomad4 OTH exome

AF:

0.0000689

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000378

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

Jan 10, 2022

The c.955C>T (p.R319W) alteration is located in exon 7 (coding exon 6) of the AGBL3 gene. This alteration results from a C to T substitution at nucleotide position 955, causing the arginine (R) at amino acid position 319 to be replaced by a tryptophan (W). 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

-0.27

BayesDel_noAF

Benign

-0.31

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Benign

-0.053

FATHMM_MKL

Benign

0.080

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;.

Vest4

0.34

MVP

0.22

ClinPred

0.45

GERP RS

2.6

gMVP

0.64

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