chr4-183691323-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021942.6(TRAPPC11):āc.1901A>Gā(p.Asn634Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000513 in 1,515,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.00025 ( 0 hom., cov: 32)
Exomes š: 0.00054 ( 0 hom. )
Consequence
TRAPPC11
NM_021942.6 missense
NM_021942.6 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 7.10
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2743297).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC11 | NM_021942.6 | c.1901A>G | p.Asn634Ser | missense_variant | 19/30 | ENST00000334690.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC11 | ENST00000334690.11 | c.1901A>G | p.Asn634Ser | missense_variant | 19/30 | 1 | NM_021942.6 | P1 | |
TRAPPC11 | ENST00000357207.8 | c.1901A>G | p.Asn634Ser | missense_variant | 19/31 | 1 | |||
TRAPPC11 | ENST00000512476.1 | c.719A>G | p.Asn240Ser | missense_variant | 8/19 | 1 | |||
TRAPPC11 | ENST00000505676.5 | c.*15A>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/19 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000155 AC: 36AN: 232168Hom.: 0 AF XY: 0.000143 AC XY: 18AN XY: 125600
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GnomAD4 exome AF: 0.000542 AC: 739AN: 1363022Hom.: 0 Cov.: 30 AF XY: 0.000520 AC XY: 350AN XY: 672972
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GnomAD4 genome AF: 0.000250 AC: 38AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 07, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31597922, 28404951, 27270441) - |
Autosomal recessive limb-girdle muscular dystrophy type R18 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 634 of the TRAPPC11 protein (p.Asn634Ser). This variant is present in population databases (rs148567547, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TRAPPC11-related conditions. ClinVar contains an entry for this variant (Variation ID: 448694). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TRAPPC11 protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 05, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.1901A>G (p.N634S) alteration is located in exon 19 (coding exon 18) of the TRAPPC11 gene. This alteration results from a A to G substitution at nucleotide position 1901, causing the asparagine (N) at amino acid position 634 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
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
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D
REVEL
Uncertain
Sift
Benign
D;D;D
Sift4G
Benign
T;T;D
Polyphen
D;P;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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