rs149504969
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001160372.4(TRAPPC9):c.543G>A(p.Pro181Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,612,984 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 4 hom. )
Consequence
TRAPPC9
NM_001160372.4 synonymous
NM_001160372.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.24
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 8-140450831-C-T is Benign according to our data. Variant chr8-140450831-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 437039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-6.24 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000177 (27/152226) while in subpopulation SAS AF= 0.00187 (9/4822). AF 95% confidence interval is 0.000974. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRAPPC9 | NM_001160372.4 | c.543G>A | p.Pro181Pro | synonymous_variant | 2/23 | ENST00000438773.4 | NP_001153844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRAPPC9 | ENST00000438773.4 | c.543G>A | p.Pro181Pro | synonymous_variant | 2/23 | 1 | NM_001160372.4 | ENSP00000405060.3 | ||
TRAPPC9 | ENST00000520857.5 | c.99G>A | p.Pro33Pro | synonymous_variant | 1/21 | 1 | ENSP00000430116.1 | |||
TRAPPC9 | ENST00000648948.2 | c.543G>A | p.Pro181Pro | synonymous_variant | 2/23 | ENSP00000498020.1 |
Frequencies
GnomAD3 genomes AF: 0.000178 AC: 27AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000385 AC: 96AN: 249368Hom.: 2 AF XY: 0.000475 AC XY: 64AN XY: 134842
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GnomAD4 exome AF: 0.000262 AC: 383AN: 1460758Hom.: 4 Cov.: 31 AF XY: 0.000328 AC XY: 238AN XY: 726534
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GnomAD4 genome AF: 0.000177 AC: 27AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74426
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 02, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | TRAPPC9: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 22, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 24, 2020 | 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
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 13, 2024 | This variant is classified as likely 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
RBP_binding_hub_radar
RBP_regulation_power_radar
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