chr18-31849702-T-C

Variant names:

• chr18-31849702-T-C
• rs1178309356
• NM_014939.5:c.3599A>G

Variant summary

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

The NM_014939.5(TRAPPC8):​c.3599A>G​(p.Tyr1200Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Y1200F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC8 NM_014939.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06
• 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.3599A>G	p.Tyr1200Cys	missense	Exon 25 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.3599A>G	p.Tyr1200Cys	missense	Exon 25 of 29	ENSP00000283351.4	Q9Y2L5-1
	TRAPPC8	ENST00000582539.5	TSL:1	c.3437A>G	p.Tyr1146Cys	missense	Exon 25 of 29	ENSP00000463764.1	J3QQJ5
	TRAPPC8	ENST00000865828.1		c.3602A>G	p.Tyr1201Cys	missense	Exon 25 of 29	ENSP00000535887.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.045	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.13
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.73	P
Vest4		0.66
MutPred		0.42		Gain of disorder (P = 0.0657)
MVP		0.043
MPC		0.46
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.20
gMVP		0.60
Mutation Taster		=85/15	polymorphism

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

dbSNP: rs1178309356; hg19: chr18-29429665;