chr19-7682456-C-G

Variant names:

• chr19-7682456-C-G
• NM_001042462.2:c.203C>G

Variant summary

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

The NM_001042462.2(TRAPPC5):​c.203C>G​(p.Ala68Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15206322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2	c.203C>G	p.Ala68Gly	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1
TRAPPC5	NM_001042461.3	c.203C>G	p.Ala68Gly	missense_variant	Exon 2 of 2		NP_001035926.1
TRAPPC5	NM_174894.3	c.203C>G	p.Ala68Gly	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.203C>G	p.Ala68Gly	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1
ENSG00000269711	ENST00000597959.1	c.378C>G	p.Cys126Trp	missense_variant	Exon 3 of 3	4		ENSP00000469811.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.203C>G (p.A68G) alteration is located in exon 2 (coding exon 1) of the TRAPPC5 gene. This alteration results from a C to G substitution at nucleotide position 203, causing the alanine (A) at amino acid position 68 to be replaced by a glycine (G). 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	0.099
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.88	.;.;D
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	.;D;D
REVEL	Benign	0.090
Sift	Uncertain	0.0070	.;D;D
Sift4G	Uncertain	0.043	D;D;D
Polyphen		0.0020	B;B;B
Vest4		0.099
MutPred		0.56		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.043
MPC		1.2
ClinPred		0.48	T
GERP RS		0.30
Varity_R		0.32
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr19-7747342;