17-7931034-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC1	NM_021210.5	c.286G>T	p.Val96Leu	missense_variant	Exon 3 of 4	ENST00000303731.9	NP_067033.1
TRAPPC1	NM_001166621.1	c.286G>T	p.Val96Leu	missense_variant	Exon 4 of 5		NP_001160093.1
TRAPPC1	NR_030684.2	n.332G>T		non_coding_transcript_exon_variant	Exon 2 of 3
TRAPPC1	NR_030697.1	n.275G>T		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC1	ENST00000303731.9	c.286G>T	p.Val96Leu	missense_variant	Exon 3 of 4	1	NM_021210.5	ENSP00000302783.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286G>T (p.V96L) alteration is located in exon 3 (coding exon 3) of the TRAPPC1 gene. This alteration results from a G to T substitution at nucleotide position 286, causing the valine (V) at amino acid position 96 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.47	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.11	N;N
REVEL	Benign	0.28
Sift	Benign	1.0	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.0	B;B
Vest4		0.39
MutPred		0.52		Gain of catalytic residue at V96 (P = 0.0013);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7834352;