1-48539690-C-T

Variant summary

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

The NM_032785.4(AGBL4):​c.1316G>A​(p.Arg439Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,543,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

AGBL4
NM_032785.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44
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]

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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=0.087412894).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGBL4NM_032785.4 linkuse as main transcriptc.1316G>A p.Arg439Gln missense_variant 12/14 ENST00000371839.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGBL4ENST00000371839.6 linkuse as main transcriptc.1316G>A p.Arg439Gln missense_variant 12/142 NM_032785.4 P1Q5VU57-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
151994
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000325
AC:
5
AN:
153760
Hom.:
0
AF XY:
0.0000369
AC XY:
3
AN XY:
81252
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000841
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000448
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000334
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000280
AC:
39
AN:
1391854
Hom.:
0
Cov.:
30
AF XY:
0.0000321
AC XY:
22
AN XY:
686032
show subpopulations
Gnomad4 AFR exome
AF:
0.0000961
Gnomad4 AMR exome
AF:
0.0000566
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000283
Gnomad4 SAS exome
AF:
0.0000383
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000279
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
151994
Hom.:
0
Cov.:
32
AF XY:
0.0000674
AC XY:
5
AN XY:
74224
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491

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 submitterclinical testingAmbry GeneticsOct 05, 2021The c.1316G>A (p.R439Q) alteration is located in exon 12 (coding exon 12) of the AGBL4 gene. This alteration results from a G to A substitution at nucleotide position 1316, causing the arginine (R) at amino acid position 439 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
Benign
0.13
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.56
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0059
T;.
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.64
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.087
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
L;.
MutationTaster
Benign
0.87
N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.69
N;.
REVEL
Benign
0.051
Sift
Benign
0.12
T;.
Sift4G
Benign
0.24
T;T
Polyphen
0.15
B;.
Vest4
0.33
MutPred
0.41
Loss of MoRF binding (P = 0.0169);.;
MVP
0.030
MPC
0.15
ClinPred
0.060
T
GERP RS
3.9
Varity_R
0.051
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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.

Other links and lift over

dbSNP: rs956099366; hg19: chr1-49005362; API