X-13714442-CT-C

Position:

• chrX-13714442-CT-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_001011658.4(TRAPPC2):​c.387delA​(p.Val130fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: TRAPPC2 NM_001011658.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.08

Genes affected

TRAPPC2 (HGNC:23068): (trafficking protein particle complex subunit 2) The protein encoded by this gene is thought to be part of a large multi-subunit complex involved in the targeting and fusion of endoplasmic reticulum-to-Golgi transport vesicles with their acceptor compartment. In addition, the encoded protein can bind c-myc promoter-binding protein 1 and block its transcriptional repression capability. Mutations in this gene are a cause of spondyloepiphyseal dysplasia tarda (SEDT). A processed pseudogene of this gene is located on chromosome 19, and other pseudogenes are found on chromosomes 8 and Y. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0851 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-13714442-CT-C is Pathogenic according to our data. Variant chrX-13714442-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 11517.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4	c.387delA	p.Val130fs	frameshift_variant	6/6	ENST00000380579.6	NP_001011658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC2	ENST00000380579.6	c.387delA	p.Val130fs	frameshift_variant	6/6	1	NM_001011658.4	ENSP00000369953.1
TRAPPC2	ENST00000683983.1	c.489delA	p.Val164fs	frameshift_variant	6/6			ENSP00000507474.1
TRAPPC2	ENST00000359680.9	c.387delA	p.Val130fs	frameshift_variant	5/5	1		ENSP00000352708.5
TRAPPC2	ENST00000458511.7	c.387delA	p.Val130fs	frameshift_variant	6/6	5		ENSP00000392495.3
TRAPPC2	ENST00000518847.2	c.387delA	p.Val130fs	frameshift_variant	5/5	4		ENSP00000428900.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spondyloepiphyseal dysplasia tarda Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 15, 2004

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs587776754; hg19: chrX-13732561;