19-7682306-C-A

Variant names:

• chr19-7682306-C-A
• rs758155361
• NM_001042462.2:c.53C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042462.2(TRAPPC5):​c.53C>A​(p.Ala18Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. A18V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10250816).

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.53C>A	p.Ala18Glu	missense	Exon 2 of 2	NP_001035927.1	Q8IUR0
	TRAPPC5	NM_001042461.3		c.53C>A	p.Ala18Glu	missense	Exon 2 of 2	NP_001035926.1	Q8IUR0
	TRAPPC5	NM_174894.3		c.53C>A	p.Ala18Glu	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.53C>A	p.Ala18Glu	missense	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
	TRAPPC5	ENST00000317378.5	TSL:1	c.53C>A	p.Ala18Glu	missense	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
	ENSG00000269711	ENST00000597959.1	TSL:4	c.228C>A	p.Gly76Gly	synonymous	Exon 3 of 3	ENSP00000469811.1	M0QYG6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333280 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 656012

African (AFR) AF: 0.0000385 AC: 1 AN: 25970

American (AMR) AF: 0.00 AC: 0 AN: 21814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21054

East Asian (EAS) AF: 0.00 AC: 0 AN: 32720

South Asian (SAS) AF: 0.00 AC: 0 AN: 69124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4474

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057960

Other (OTH) AF: 0.00 AC: 0 AN: 54948

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.078
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.020
Sift	Benign	0.030	D
Sift4G	Benign	0.44	T
Polyphen		0.19	B
Vest4		0.10
MutPred		0.32		Gain of disorder (P = 0.0452)
MVP		0.043
MPC		1.4
ClinPred		0.23	T
GERP RS		-1.5
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.69
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs758155361; hg19: chr19-7747192;