6-116500539-C-G

Variant names:

• chr6-116500539-C-G
• rs368049149
• NM_001139444.3:c.368G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001139444.3(TRAPPC3L):​c.368G>C​(p.Arg123Pro) 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. 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. R123Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC3L NM_001139444.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

Genes affected

TRAPPC3L (HGNC:21090): (trafficking protein particle complex subunit 3L) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and intra-Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36237028).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139444.3. 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
	TRAPPC3L	NM_001139444.3	MANE Select	c.368G>C	p.Arg123Pro	missense	Exon 4 of 5	NP_001132916.1	Q5T215-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC3L	ENST00000368602.4	TSL:5 MANE Select	c.368G>C	p.Arg123Pro	missense	Exon 4 of 5	ENSP00000357591.3	Q5T215-1
	TRAPPC3L	ENST00000437098.5	TSL:3	c.326G>C	p.Arg109Pro	missense	Exon 3 of 4	ENSP00000395769.1	A0A0A0MSL6
	TRAPPC3L	ENST00000356128.4	TSL:2	c.116G>C	p.Arg39Pro	missense	Exon 2 of 3	ENSP00000348445.4	Q5T215-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.18
Sift	Benign	0.29	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.45		Gain of glycosylation at R123 (P = 0.0222)
MVP		0.20
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.92
gMVP		0.60
Mutation Taster		=52/48	polymorphism

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

dbSNP: rs368049149; hg19: chr6-116821702;