rs1135401749
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_016030.6(TRAPPC12):c.360dup(p.Glu121ArgfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000454 in 1,322,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000045 ( 0 hom. )
Consequence
TRAPPC12
NM_016030.6 frameshift
NM_016030.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.28
Genes affected
TRAPPC12 (HGNC:24284): (trafficking protein particle complex subunit 12) Involved in several processes, including endoplasmic reticulum to Golgi vesicle-mediated transport; positive regulation of protein localization to kinetochore; and regulation of kinetochore assembly. Located in Golgi apparatus; kinetochore; and nucleoplasm. Part of TRAPP complex. Colocalizes with endoplasmic reticulum-Golgi intermediate compartment and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-3387978-G-GC is Pathogenic according to our data. Variant chr2-3387978-G-GC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 430822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC12 | NM_016030.6 | c.360dup | p.Glu121ArgfsTer7 | frameshift_variant | 2/12 | ENST00000324266.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC12 | ENST00000324266.10 | c.360dup | p.Glu121ArgfsTer7 | frameshift_variant | 2/12 | 1 | NM_016030.6 | P1 | |
TRAPPC12 | ENST00000382110.6 | c.360dup | p.Glu121ArgfsTer7 | frameshift_variant | 2/12 | 2 | P1 | ||
TRAPPC12 | ENST00000482645.1 | n.521dup | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000454 AC: 6AN: 1322730Hom.: 0 Cov.: 30 AF XY: 0.00000462 AC XY: 3AN XY: 649712
GnomAD4 exome
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1322730
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30
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3
AN XY:
649712
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
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Cov.:
33
Bravo
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 18, 2017 | - - |
Progressive childhood encephalopathy Pathogenic:1
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | May 01, 2017 | - - |
TRAPPC12-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 17, 2024 | The TRAPPC12 c.360dupC variant is predicted to result in a frameshift and premature protein termination (p.Glu121Argfs*7). This variant has been reported in the compound heterozygous state in two siblings with progressive childhood encephalopathy and golgi dysfunction (Milev et al. 2017. PubMed ID: 28777934). This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in TRAPPC12 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
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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