chr4-183684206-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_021942.6(TRAPPC11):​c.1349G>C​(p.Arg450Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

TRAPPC11
NM_021942.6 missense

Scores

13
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.96
Variant links:
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRAPPC11NM_021942.6 linkuse as main transcriptc.1349G>C p.Arg450Pro missense_variant 13/30 ENST00000334690.11 NP_068761.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRAPPC11ENST00000334690.11 linkuse as main transcriptc.1349G>C p.Arg450Pro missense_variant 13/301 NM_021942.6 ENSP00000335371 P1Q7Z392-1
TRAPPC11ENST00000357207.8 linkuse as main transcriptc.1349G>C p.Arg450Pro missense_variant 13/311 ENSP00000349738 Q7Z392-3
TRAPPC11ENST00000512476.1 linkuse as main transcriptc.167G>C p.Arg56Pro missense_variant 2/191 ENSP00000421004
TRAPPC11ENST00000505676.5 linkuse as main transcriptc.348+200G>C intron_variant, NMD_transcript_variant 1 ENSP00000422915

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.49
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D;.;T
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.97
D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.87
D;D;D
MetaSVM
Uncertain
0.22
D
MutationAssessor
Uncertain
2.6
M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-6.1
D;D;D
REVEL
Pathogenic
0.68
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.99
MutPred
0.50
Loss of MoRF binding (P = 0.0039);Loss of MoRF binding (P = 0.0039);.;
MVP
0.43
MPC
0.84
ClinPred
1.0
D
GERP RS
5.7
Varity_R
0.96
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201387237; hg19: chr4-184605359; API