TRAPPC3 p.Phe167Leu

Variant names:

• chr1-36137245-G-T
• NM_014408.5:c.501C>A
• TRAPPC3 p.Phe167Leu

Your query was ambiguous. Multiple possible variants found:

• chr1-36137245-G-T
• chr1-36137245-G-C
• chr1-36137247-A-G
• chr1-36137245-GAA-AAG
• chr1-36137245-GAA-TAG
• chr1-36137245-GAA-CAG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_014408.5(TRAPPC3):​c.501C>A​(p.Phe167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC3 NM_014408.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

Genes affected

TRAPPC3 (HGNC:19942): (trafficking protein particle complex subunit 3) This gene encodes a component of the trafficking protein particle complex, which tethers transport vesicles to the cis-Golgi membrane. The encoded protein participates in the regulation of transport from the endoplasmic reticulum to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.2034 (below the threshold of 3.09). Trascript score misZ: 0.88837 (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014408.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC3	NM_014408.5	MANE Select	c.501C>A	p.Phe167Leu	missense	Exon 5 of 5	NP_055223.1	O43617-1
	TRAPPC3	NM_001270894.2		c.525C>A	p.Phe175Leu	missense	Exon 5 of 5	NP_001257823.1	A0A087WWM0
	TRAPPC3	NM_001270895.2		c.363C>A	p.Phe121Leu	missense	Exon 5 of 5	NP_001257824.1	O43617-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC3	ENST00000373166.8	TSL:1 MANE Select	c.501C>A	p.Phe167Leu	missense	Exon 5 of 5	ENSP00000362261.3	O43617-1
	TRAPPC3	ENST00000923688.1		c.546C>A	p.Phe182Leu	missense	Exon 5 of 5	ENSP00000593747.1
	TRAPPC3	ENST00000616395.4	TSL:3	c.525C>A	p.Phe175Leu	missense	Exon 5 of 5	ENSP00000480332.1	A0A087WWM0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0049	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		3.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.24
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.59
gMVP		0.75
Mutation Taster		=3/97	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-36602846;