chr15-86258030-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2
The NM_001386094.1(AGBL1):c.968A>G(p.Glu323Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000144 in 1,613,546 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 2 hom. )
Consequence
AGBL1
NM_001386094.1 missense, splice_region
NM_001386094.1 missense, splice_region
Scores
1
3
10
Splicing: ADA: 0.9990
2
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
AGBL1 (HGNC:26504): (AGBL carboxypeptidase 1) Polyglutamylation is a reversible posttranslational modification catalyzed by polyglutamylases that results in the addition of glutamate side chains on the modified protein. This gene encodes a glutamate decarboxylase that catalyzes the deglutamylation of polyglutamylated proteins. Mutations in this gene result in dominant late-onset Fuchs corneal dystrophy. [provided by RefSeq, Nov 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BP6
?
Variant 15-86258030-A-G is Benign according to our data. Variant chr15-86258030-A-G is described in ClinVar as [Benign]. Clinvar id is 3057355.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 37 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGBL1 | NM_001386094.1 | c.968A>G | p.Glu323Gly | missense_variant, splice_region_variant | 9/23 | ENST00000614907.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGBL1 | ENST00000614907.3 | c.968A>G | p.Glu323Gly | missense_variant, splice_region_variant | 9/23 | 5 | NM_001386094.1 | P4 | |
AGBL1 | ENST00000441037.7 | c.968A>G | p.Glu323Gly | missense_variant, splice_region_variant | 9/25 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152214Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
37
AN:
152214
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000675 AC: 168AN: 248786Hom.: 2 AF XY: 0.000615 AC XY: 83AN XY: 134980
GnomAD3 exomes
AF:
AC:
168
AN:
248786
Hom.:
AF XY:
AC XY:
83
AN XY:
134980
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000133 AC: 195AN: 1461214Hom.: 2 Cov.: 30 AF XY: 0.000114 AC XY: 83AN XY: 726900
GnomAD4 exome
AF:
AC:
195
AN:
1461214
Hom.:
Cov.:
30
AF XY:
AC XY:
83
AN XY:
726900
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74486
GnomAD4 genome
?
AF:
AC:
37
AN:
152332
Hom.:
Cov.:
32
AF XY:
AC XY:
20
AN XY:
74486
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
74
Asia WGS
AF:
AC:
5
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
AGBL1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 09, 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
REVEL
Benign
Polyphen
0.96
.;D
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at