chr17-7931034-C-A

Variant names:

• chr17-7931034-C-A
• NM_021210.5:c.286G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021210.5(TRAPPC1):​c.286G>T​(p.Val96Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRAPPC1 NM_021210.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06
• Publications: 0 publications found

Genes affected

TRAPPC1 (HGNC:19894): (trafficking protein particle complex subunit 1) This gene product plays a role in vesicular transport of proteins to the Golgi apparatus from the endoplasmic reticulum. The encoded protein is a component of the multisubunit transport protein particle (TRAPP) complex. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2512558).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021210.5. 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
	TRAPPC1	NM_021210.5	MANE Select	c.286G>T	p.Val96Leu	missense	Exon 3 of 4	NP_067033.1	Q9Y5R8
	TRAPPC1	NM_001166621.1		c.286G>T	p.Val96Leu	missense	Exon 4 of 5	NP_001160093.1	Q9Y5R8
	TRAPPC1	NR_030684.2		n.332G>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC1	ENST00000303731.9	TSL:1 MANE Select	c.286G>T	p.Val96Leu	missense	Exon 3 of 4	ENSP00000302783.4	Q9Y5R8
	TRAPPC1	ENST00000540486.5	TSL:2	c.286G>T	p.Val96Leu	missense	Exon 4 of 5	ENSP00000441130.1	Q9Y5R8
	TRAPPC1	ENST00000968005.1		c.283G>T	p.Val95Leu	missense	Exon 3 of 4	ENSP00000638064.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.64
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.47	N
PhyloP100		4.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.28
Sift	Benign	1.0	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.39
MutPred		0.52		Gain of catalytic residue at V96 (P = 0.0013)
MVP		0.61
MPC		0.77
ClinPred		0.24	T
GERP RS		3.4
Varity_R		0.066
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr17-7834352;