15-86262793-A-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001386094.1(AGBL1):c.985A>T(p.Thr329Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000392 in 1,606,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
AGBL1
NM_001386094.1 missense
NM_001386094.1 missense
Scores
3
1
10
Clinical Significance
Conservation
PhyloP100: 6.83
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27953494).
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGBL1 | NM_001386094.1 | c.985A>T | p.Thr329Ser | missense_variant | 10/23 | ENST00000614907.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGBL1 | ENST00000614907.3 | c.985A>T | p.Thr329Ser | missense_variant | 10/23 | 5 | NM_001386094.1 | P4 | |
AGBL1 | ENST00000568785.5 | n.169A>T | non_coding_transcript_exon_variant | 1/8 | 1 | ||||
AGBL1 | ENST00000441037.7 | c.985A>T | p.Thr329Ser | missense_variant | 10/25 | 5 | A2 | ||
AGBL1 | ENST00000567715.1 | n.59A>T | non_coding_transcript_exon_variant | 2/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152162Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000208 AC: 5AN: 240472Hom.: 0 AF XY: 0.0000308 AC XY: 4AN XY: 129868
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GnomAD4 exome AF: 0.0000413 AC: 60AN: 1454124Hom.: 0 Cov.: 28 AF XY: 0.0000526 AC XY: 38AN XY: 722604
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2021 | The c.847A>T (p.T283S) alteration is located in exon 9 (coding exon 8) of the AGBL1 gene. This alteration results from a A to T substitution at nucleotide position 847, causing the threonine (T) at amino acid position 283 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Corneal dystrophy, Fuchs endothelial, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
REVEL
Benign
Polyphen
0.95
.;P
MutPred
0.11
.;Gain of helix (P = 0.0425);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at