4-183693144-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_021942.6(TRAPPC11):c.2234C>A(p.Thr745Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000556 in 1,583,534 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T745I) has been classified as Uncertain significance.
Frequency
Consequence
NM_021942.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC11 | NM_021942.6 | c.2234C>A | p.Thr745Lys | missense_variant | 20/30 | ENST00000334690.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC11 | ENST00000334690.11 | c.2234C>A | p.Thr745Lys | missense_variant | 20/30 | 1 | NM_021942.6 | P1 | |
TRAPPC11 | ENST00000357207.8 | c.2234C>A | p.Thr745Lys | missense_variant | 20/31 | 1 | |||
TRAPPC11 | ENST00000512476.1 | c.1052C>A | p.Thr351Lys | missense_variant | 9/19 | 1 | |||
TRAPPC11 | ENST00000505676.5 | c.*348C>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/19 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000172 AC: 4AN: 232326Hom.: 0 AF XY: 0.0000318 AC XY: 4AN XY: 125740
GnomAD4 exome AF: 0.0000566 AC: 81AN: 1431396Hom.: 0 Cov.: 30 AF XY: 0.0000550 AC XY: 39AN XY: 708628
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 19, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34648194) - |
Autosomal recessive limb-girdle muscular dystrophy type R18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces threonine with lysine at codon 745 of the TRAPPC11 protein (p.Thr745Lys). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and lysine. This variant is present in population databases (rs768000138, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with TRAPPC11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at