19-7682684-C-T

Variant names:

• chr19-7682684-C-T
• NM_001042462.2:c.431C>T

Variant summary

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

The NM_001042462.2(TRAPPC5):​c.431C>T​(p.Ala144Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2	c.431C>T	p.Ala144Val	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1
TRAPPC5	NM_001042461.3	c.431C>T	p.Ala144Val	missense_variant	Exon 2 of 2		NP_001035926.1
TRAPPC5	NM_174894.3	c.431C>T	p.Ala144Val	missense_variant	Exon 2 of 2		NP_777554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC5	ENST00000596148.3	c.431C>T	p.Ala144Val	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1
ENSG00000269711	ENST00000597959.1	c.*195C>T		3_prime_UTR_variant	Exon 3 of 3	4		ENSP00000469811.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.431C>T (p.A144V) alteration is located in exon 2 (coding exon 1) of the TRAPPC5 gene. This alteration results from a C to T substitution at nucleotide position 431, causing the alanine (A) at amino acid position 144 to be replaced by a valine (V). 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	Pathogenic	0.95
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.96	.;.;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.3	M;M;M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.7	.;D;D;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.59
MutPred		0.83		Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);.;
MVP		0.27
MPC		2.2
ClinPred		0.99	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: -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: chr19-7747570;