4-183705044-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021942.6(TRAPPC11):c.3029A>T(p.Glu1010Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 1,594,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
TRAPPC11
NM_021942.6 missense
NM_021942.6 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 8.73
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.3029A>T | p.Glu1010Val | missense_variant | 27/30 | ENST00000334690.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC11 | ENST00000334690.11 | c.3029A>T | p.Glu1010Val | missense_variant | 27/30 | 1 | NM_021942.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251392Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135852
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GnomAD4 exome AF: 0.0000291 AC: 42AN: 1441986Hom.: 0 Cov.: 29 AF XY: 0.0000293 AC XY: 21AN XY: 717454
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2023 | The c.3029A>T (p.E1010V) alteration is located in exon 27 (coding exon 26) of the TRAPPC11 gene. This alteration results from a A to T substitution at nucleotide position 3029, causing the glutamic acid (E) at amino acid position 1010 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive limb-girdle muscular dystrophy type R18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2021 | This sequence change replaces glutamic acid with valine at codon 1010 of the TRAPPC11 protein (p.Glu1010Val). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and valine. This variant is present in population databases (rs773678506, ExAC 0.003%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;P;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at