rs780631499
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001330701.2(AGTPBP1):c.2736del(p.Tyr912Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,610,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
AGTPBP1
NM_001330701.2 frameshift
NM_001330701.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.780
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 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-85588464-CG-C is Pathogenic according to our data. Variant chr9-85588464-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 522817.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.2736del | p.Tyr912Ter | frameshift_variant | 21/26 | ENST00000357081.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGTPBP1 | ENST00000357081.8 | c.2736del | p.Tyr912Ter | frameshift_variant | 21/26 | 5 | NM_001330701.2 | P1 | |
AGTPBP1 | ENST00000376083.7 | c.2616del | p.Tyr872Ter | frameshift_variant | 21/26 | 1 | |||
AGTPBP1 | ENST00000337006.8 | c.2892del | p.Tyr964Ter | frameshift_variant | 20/25 | 5 | |||
AGTPBP1 | ENST00000628899.1 | c.2772del | p.Tyr924Ter | frameshift_variant | 20/25 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152016Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247630Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133940
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GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458404Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725482
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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
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at