2-3387767-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016030.6(TRAPPC12):c.145del(p.Glu49ArgfsTer14) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
TRAPPC12
NM_016030.6 frameshift
NM_016030.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.27
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 12 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 2-3387767-CG-C is Pathogenic according to our data. Variant chr2-3387767-CG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438738.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC12 | NM_016030.6 | c.145del | p.Glu49ArgfsTer14 | frameshift_variant | 2/12 | ENST00000324266.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC12 | ENST00000324266.10 | c.145del | p.Glu49ArgfsTer14 | frameshift_variant | 2/12 | 1 | NM_016030.6 | P1 | |
TRAPPC12 | ENST00000382110.6 | c.145del | p.Glu49ArgfsTer14 | frameshift_variant | 2/12 | 2 | P1 | ||
TRAPPC12 | ENST00000482645.1 | n.306del | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 18, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Hadassah Hebrew University Medical Center | Jun 20, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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