rs200936990
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021942.6(TRAPPC11):c.2744C>G(p.Thr915Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T915M) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
TRAPPC11
NM_021942.6 missense
NM_021942.6 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 4.53
Genes affected
TRAPPC11 (HGNC:25751): (trafficking protein particle complex subunit 11) The protein encoded by this gene is a subunit of the TRAPP (transport protein particle) tethering complex, which functions in intracellular vesicle trafficking. This subunit is involved in early stage endoplasmic reticulum-to-Golgi vesicle transport. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC11 | NM_021942.6 | c.2744C>G | p.Thr915Arg | missense_variant | 25/30 | ENST00000334690.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC11 | ENST00000334690.11 | c.2744C>G | p.Thr915Arg | missense_variant | 25/30 | 1 | NM_021942.6 | P1 | |
TRAPPC11 | ENST00000357207.8 | c.2744C>G | p.Thr915Arg | missense_variant | 25/31 | 1 | |||
TRAPPC11 | ENST00000512476.1 | c.1562C>G | p.Thr521Arg | missense_variant | 14/19 | 1 | |||
TRAPPC11 | ENST00000505676.5 | c.*858C>G | 3_prime_UTR_variant, NMD_transcript_variant | 13/19 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type R18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2016 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TRAPPC11-related disease. This sequence change replaces threonine with arginine at codon 915 of the TRAPPC11 protein (p.Thr915Arg). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and arginine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D
REVEL
Benign
Sift
Benign
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;P
Vest4
MutPred
Gain of helix (P = 0.0861);Gain of helix (P = 0.0861);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 46
Find out detailed SpliceAI scores and Pangolin per-transcript scores at