18-31830814-C-T

Variant names:

• chr18-31830814-C-T
• NM_014939.5:c.4249G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014939.5(TRAPPC8):​c.4249G>A​(p.Val1417Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRAPPC8 NM_014939.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048685282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC8	NM_014939.5	c.4249G>A	p.Val1417Met	missense_variant	Exon 29 of 29	ENST00000283351.10	NP_055754.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC8	ENST00000283351.10	c.4249G>A	p.Val1417Met	missense_variant	Exon 29 of 29	1	NM_014939.5	ENSP00000283351.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.0011	T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.46	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.18	N;.
REVEL	Benign	0.054
Sift	Benign	0.27	T;.
Sift4G	Benign	0.31	T;T
Polyphen		0.0020	B;.
Vest4		0.041
MutPred		0.25		Loss of sheet (P = 0.0457);.;
MVP		0.043
MPC		0.12
ClinPred		0.19	T
GERP RS		3.8
Varity_R		0.034
gMVP		0.10

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-29410777;