8-139732033-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_001160372.4(TRAPPC9):c.3225C>A(p.Tyr1075*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,603,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001160372.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000174 AC: 4AN: 230478Hom.: 0 AF XY: 0.0000161 AC XY: 2AN XY: 124556
GnomAD4 exome AF: 0.00000551 AC: 8AN: 1451714Hom.: 0 Cov.: 32 AF XY: 0.00000832 AC XY: 6AN XY: 721034
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Tyr1173*) in the TRAPPC9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRAPPC9 are known to be pathogenic (PMID: 2000476, 20004763, 20004764). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TRAPPC9-related conditions. ClinVar contains an entry for this variant (Variation ID: 589347). For these reasons, this variant has been classified as Pathogenic. -
not specified Uncertain:1
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Inborn genetic diseases Uncertain:1
The p.Y1173* variant (also known as c.3519C>A), located in coding exon 22 of the TRAPPC9 gene, results from a C to A substitution at nucleotide position 3519. This changes the amino acid from a tyrosine to a stop codon within coding exon 22. Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of TRAPPC9, is not expected to trigger nonsense-mediated mRNA decay, and removes only the last 74 amino acids of the protein. The exact functional impact of these removed amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at