Variant chr1-48663232-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_032785.4(AGBL4):c.644G>A(p.Arg215Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,613,756 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.022 ( 110 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 116 hom. )

Consequence

AGBL4
NM_032785.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.902

Variant links:

Genes affected

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

AGBL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014713407).

BP6

Variant 1-48663232-C-T is Benign according to our data. Variant chr1-48663232-C-T is described in ClinVar as [Benign]. Clinvar id is 3055894.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	7/14	ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	7/14	2	NM_032785.4	P1	Q5VU57-1
AGBL4	ENST00000416121.5 linkuse as main transcript	c.182G>A	p.Arg61Gln	missense_variant	3/7	1
AGBL4	ENST00000371838.5 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	7/9	5

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3326

AN:

152004

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0743

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00549

AC:

1367

AN:

249200

Hom.:

AF XY:

0.00419

AC XY:

567

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.0737

Gnomad AMR exome

AF:

0.00472

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000328

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00235

AC:

3441

AN:

1461636

Hom.:

116

Cov.:

AF XY:

0.00207

AC XY:

1502

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.0774

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.00532

GnomAD4 genome

AF:

0.0219

AC:

3336

AN:

152120

Hom.:

110

Cov.:

AF XY:

0.0217

AC XY:

1615

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0744

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.0242

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0666

AC:

262

ESP6500EA

AF:

0.000482

AC:

ExAC

AF:

0.00654

AC:

790

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AGBL4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0027

T;.;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.10

N;.;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.82

N;.;N

REVEL

Benign

0.0070

Sift

Benign

0.64

T;.;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0070

B;.;.

Vest4

0.19

MVP

0.030

MPC

0.15

ClinPred

0.010

GERP RS

2.6

Varity_R

0.039

gMVP

0.23

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