chr8-139732122-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001160372.4(TRAPPC9):c.3136C>T(p.Arg1046Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,605,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1046Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001160372.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC9 | NM_001160372.4 | c.3136C>T | p.Arg1046Trp | missense_variant | 22/23 | ENST00000438773.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC9 | ENST00000438773.4 | c.3136C>T | p.Arg1046Trp | missense_variant | 22/23 | 1 | NM_001160372.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152192Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000279 AC: 65AN: 232652Hom.: 0 AF XY: 0.000277 AC XY: 35AN XY: 126514
GnomAD4 exome AF: 0.000115 AC: 167AN: 1453576Hom.: 0 Cov.: 32 AF XY: 0.000127 AC XY: 92AN XY: 722390
GnomAD4 genome AF: 0.000145 AC: 22AN: 152192Hom.: 0 Cov.: 34 AF XY: 0.0000942 AC XY: 7AN XY: 74344
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 25, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2021 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 03, 2016 | - - |
Intellectual disability, autosomal recessive 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 28, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Intellectual Disability, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2021 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at