rs112551069
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001160372.4(TRAPPC9):c.3249C>T(p.Phe1083=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 1,596,098 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0050 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0081 ( 61 hom. )
Consequence
TRAPPC9
NM_001160372.4 synonymous
NM_001160372.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.51
Genes affected
TRAPPC9 (HGNC:30832): (trafficking protein particle complex subunit 9) This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 8-139732009-G-A is Benign according to our data. Variant chr8-139732009-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 130632.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=3, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=1.51 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.005 (762/152352) while in subpopulation NFE AF= 0.00747 (508/68032). AF 95% confidence interval is 0.00693. There are 3 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC9 | NM_001160372.4 | c.3249C>T | p.Phe1083= | synonymous_variant | 22/23 | ENST00000438773.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC9 | ENST00000438773.4 | c.3249C>T | p.Phe1083= | synonymous_variant | 22/23 | 1 | NM_001160372.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00501 AC: 762AN: 152234Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00617 AC: 1351AN: 218814Hom.: 8 AF XY: 0.00642 AC XY: 757AN XY: 117972
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GnomAD4 exome AF: 0.00810 AC: 11701AN: 1443746Hom.: 61 Cov.: 32 AF XY: 0.00801 AC XY: 5738AN XY: 716254
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GnomAD4 genome ? AF: 0.00500 AC: 762AN: 152352Hom.: 3 Cov.: 33 AF XY: 0.00460 AC XY: 343AN XY: 74496
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | TRAPPC9: BP4, BP7, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 2021 | - - |
Intellectual Disability, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 17, 2014 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
TRAPPC9-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 14, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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