19-7682549-G-A

Variant names:

• chr19-7682549-G-A
• rs201128663
• NM_001042462.2:c.296G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001042462.2(TRAPPC5):​c.296G>A​(p.Gly99Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G99V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.52
• Publications: 0 publications found

Genes affected

TRAPPC5 (HGNC:23067): (trafficking protein particle complex subunit 5) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269711 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042462.2. 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
	TRAPPC5	NM_001042462.2	MANE Select	c.296G>A	p.Gly99Asp	missense	Exon 2 of 2	NP_001035927.1	Q8IUR0
	TRAPPC5	NM_001042461.3		c.296G>A	p.Gly99Asp	missense	Exon 2 of 2	NP_001035926.1	Q8IUR0
	TRAPPC5	NM_174894.3		c.296G>A	p.Gly99Asp	missense	Exon 2 of 2	NP_777554.1	Q8IUR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC5	ENST00000596148.3	TSL:1 MANE Select	c.296G>A	p.Gly99Asp	missense	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
	TRAPPC5	ENST00000317378.5	TSL:1	c.296G>A	p.Gly99Asp	missense	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
	ENSG00000269711	ENST00000597959.1	TSL:4	c.*60G>A		3_prime_UTR	Exon 3 of 3	ENSP00000469811.1	M0QYG6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.79		Loss of MoRF binding (P = 0.0686)
MVP		0.17
MPC		2.7
ClinPred		0.99	D
GERP RS		4.1
PromoterAI		0.0042	Neutral
Varity_R		0.91
gMVP		0.93
Mutation Taster		=11/89	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

dbSNP: rs201128663; hg19: chr19-7747435;