Variant chr1-48653403-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032785.4(AGBL4):c.773G>A(p.Arg258Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000931 in 1,589,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

AGBL4
NM_032785.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL4	NM_032785.4 linkuse as main transcript	c.773G>A	p.Arg258Gln	missense_variant	8/14	ENST00000371839.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL4	ENST00000371839.6 linkuse as main transcript	c.773G>A	p.Arg258Gln	missense_variant	8/14	2	NM_032785.4	P1	Q5VU57-1
AGBL4	ENST00000416121.5 linkuse as main transcript	c.311G>A	p.Arg104Gln	missense_variant	4/7	1
AGBL4	ENST00000371838.5 linkuse as main transcript	c.773G>A	p.Arg258Gln	missense_variant	8/9	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

211810

Hom.:

AF XY:

0.0000530

AC XY:

AN XY:

113262

show subpopulations

Gnomad AFR exome

AF:

0.0000809

Gnomad AMR exome

AF:

0.0000975

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000646

Gnomad SAS exome

AF:

0.0000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000535

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

147

AN:

1437186

Hom.:

Cov.:

AF XY:

0.0000843

AC XY:

AN XY:

711916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000723

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000806

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000249

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

Oct 06, 2022

The c.773G>A (p.R258Q) alteration is located in exon 8 (coding exon 8) of the AGBL4 gene. This alteration results from a G to A substitution at nucleotide position 773, causing the arginine (R) at amino acid position 258 to be replaced by a glutamine (Q). 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

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

T;.;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.6

H;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.9

D;.;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.96

MVP

0.36

MPC

0.64

ClinPred

0.97

GERP RS

5.8

Varity_R

0.81

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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