chr18-31846747-C-T

Variant names:

• chr18-31846747-C-T
• NM_014939.5:c.3806G>A

Variant summary

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

The NM_014939.5(TRAPPC8):​c.3806G>A​(p.Gly1269Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC8 NM_014939.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.82
• Publications: 0 publications found

Genes affected

TRAPPC8 (HGNC:29169): (trafficking protein particle complex subunit 8) Involved in Golgi organization. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014939.5. 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
	TRAPPC8	NM_014939.5	MANE Select	c.3806G>A	p.Gly1269Glu	missense	Exon 26 of 29	NP_055754.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC8	ENST00000283351.10	TSL:1 MANE Select	c.3806G>A	p.Gly1269Glu	missense	Exon 26 of 29	ENSP00000283351.4	Q9Y2L5-1
	TRAPPC8	ENST00000582539.5	TSL:1	c.3644G>A	p.Gly1215Glu	missense	Exon 26 of 29	ENSP00000463764.1	J3QQJ5
	TRAPPC8	ENST00000865828.1		c.3809G>A	p.Gly1270Glu	missense	Exon 26 of 29	ENSP00000535887.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.0049	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.26
Sift	Benign	0.033	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.88
MutPred		0.43		Loss of loop (P = 0.0112)
MVP		0.068
MPC		0.58
ClinPred		0.92	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.76
Mutation Taster		=42/58	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

Other links and lift over

hg19: chr18-29426710;