rs1554699491
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PM2PP3_StrongPP5_Moderate
The NM_001330701.2(AGTPBP1):c.2336-1G>T variant causes a splice acceptor change. The variant allele was found at a frequency of 0.000000714 in 1,401,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
AGTPBP1
NM_001330701.2 splice_acceptor
NM_001330701.2 splice_acceptor
Scores
4
2
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 5.54
Genes affected
AGTPBP1 (HGNC:17258): (ATP/GTP binding carboxypeptidase 1) NNA1 is a zinc carboxypeptidase that contains nuclear localization signals and an ATP/GTP-binding motif that was initially cloned from regenerating spinal cord neurons of the mouse.[supplied by OMIM, Jul 2002]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 16 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 6.8, offset of 29, new splice context is: cactcatgtattcggttcAGgaa. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 9-85596450-C-A is Pathogenic according to our data. Variant chr9-85596450-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 522816.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGTPBP1 | NM_001330701.2 | c.2336-1G>T | splice_acceptor_variant | ENST00000357081.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGTPBP1 | ENST00000357081.8 | c.2336-1G>T | splice_acceptor_variant | 5 | NM_001330701.2 | P1 | |||
AGTPBP1 | ENST00000376083.7 | c.2216-1G>T | splice_acceptor_variant | 1 | |||||
AGTPBP1 | ENST00000337006.8 | c.2492-1G>T | splice_acceptor_variant | 5 | |||||
AGTPBP1 | ENST00000628899.1 | c.2372-1G>T | splice_acceptor_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1401462Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 696512
GnomAD4 exome
AF:
AC:
1
AN:
1401462
Hom.:
Cov.:
26
AF XY:
AC XY:
0
AN XY:
696512
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
AGTPBP1-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Undiagnosed Diseases Network, NIH | Jan 05, 2017 | This individual has been reported in PMID: 30420557. - |
Neurodegeneration, childhood-onset, with cerebellar atrophy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 11, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -30
DS_AL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at