chr1-48534246-G-A

Variant summary

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

The NM_032785.4(AGBL4):​c.1439C>T​(p.Ala480Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,551,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

AGBL4
NM_032785.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34
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=0.10092071).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGBL4NM_032785.4 linkuse as main transcriptc.1439C>T p.Ala480Val missense_variant 14/14 ENST00000371839.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGBL4ENST00000371839.6 linkuse as main transcriptc.1439C>T p.Ala480Val missense_variant 14/142 NM_032785.4 P1Q5VU57-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399410
Hom.:
0
Cov.:
30
AF XY:
0.00000145
AC XY:
1
AN XY:
690200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 GeneticsMay 04, 2023The c.1439C>T (p.A480V) alteration is located in exon 14 (coding exon 14) of the AGBL4 gene. This alteration results from a C to T substitution at nucleotide position 1439, causing the alanine (A) at amino acid position 480 to be replaced by a valine (V). 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
0.074
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0037
T;.
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.092
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.21
N;.
REVEL
Benign
0.042
Sift
Benign
0.61
T;.
Sift4G
Benign
0.18
T;T
Polyphen
0.0060
B;.
Vest4
0.058
MutPred
0.26
Loss of relative solvent accessibility (P = 0.0404);.;
MVP
0.10
MPC
0.13
ClinPred
0.23
T
GERP RS
4.0
Varity_R
0.051
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs774502535; hg19: chr1-48999918; API