4-183684206-G-C

Position:

• chr4-183684206-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R450Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC11 NM_021942.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.96

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]

ACMG classification

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	UniProt
TRAPPC11	NM_021942.6	c.1349G>C	p.Arg450Pro	missense_variant	13/30	ENST00000334690.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.1349G>C	p.Arg450Pro	missense_variant	13/30	1	NM_021942.6	P1
TRAPPC11	ENST00000357207.8	c.1349G>C	p.Arg450Pro	missense_variant	13/31	1
TRAPPC11	ENST00000512476.1	c.167G>C	p.Arg56Pro	missense_variant	2/19	1
TRAPPC11	ENST00000505676.5	c.348+200G>C		intron_variant, NMD_transcript_variant		1

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

Other links and lift over

dbSNP: rs201387237; hg19: chr4-184605359;