18-31852612-C-T

Variant names:

• chr18-31852612-C-T
• NM_014939.5:c.3485G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014939.5(TRAPPC8):​c.3485G>A​(p.Arg1162Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC8 NM_014939.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

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

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=0.076907665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC8	NM_014939.5	c.3485G>A	p.Arg1162Lys	missense_variant	Exon 23 of 29	ENST00000283351.10	NP_055754.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC8	ENST00000283351.10	c.3485G>A	p.Arg1162Lys	missense_variant	Exon 23 of 29	1	NM_014939.5	ENSP00000283351.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3485G>A (p.R1162K) alteration is located in exon 23 (coding exon 23) of the TRAPPC8 gene. This alteration results from a G to A substitution at nucleotide position 3485, causing the arginine (R) at amino acid position 1162 to be replaced by a lysine (K). 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	0.081
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.62
DEOGEN2	Benign	0.0032	T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.88
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.89	N;.
REVEL	Benign	0.094
Sift	Benign	0.34	T;.
Sift4G	Benign	0.33	T;T
Polyphen		0.034	B;.
Vest4		0.097
MutPred		0.41		Gain of methylation at R1162 (P = 0.0051);.;
MVP		0.043
MPC		0.12
ClinPred		0.13	T
GERP RS		-0.064
Varity_R		0.051
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr18-29432575;