1-36137245-GAA-AAG

Variant names:

• chr1-36137245-GAA-AAG
• NM_014408.5:c.499_501delTTCinsCTT
• TRAPPC3 p.Phe167Leu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP2 PP3

The NM_014408.5(TRAPPC3):​c.499_501delTTCinsCTT​(p.Phe167Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: 9.32
• 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 2 ACMG points.

• 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).
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.499_501delTTCinsCTT	p.Phe167Leu	missense	N/A	NP_055223.1	O43617-1
	TRAPPC3	NM_001270894.2		c.523_525delTTCinsCTT	p.Phe175Leu	missense	N/A	NP_001257823.1	A0A087WWM0
	TRAPPC3	NM_001270895.2		c.361_363delTTCinsCTT	p.Phe121Leu	missense	N/A	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.499_501delTTCinsCTT	p.Phe167Leu	missense	N/A	ENSP00000362261.3	O43617-1
	TRAPPC3	ENST00000923688.1		c.544_546delTTCinsCTT	p.Phe182Leu	missense	N/A	ENSP00000593747.1
	TRAPPC3	ENST00000616395.4	TSL:3	c.523_525delTTCinsCTT	p.Phe175Leu	missense	N/A	ENSP00000480332.1	A0A087WWM0

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

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;