X-13713103-CAAAAAA-CAAAAAAA

Variant names:

• chrX-13713103-C-CA
• rs35590746
• NM_001011658.4:c.*1303dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001011658.4(TRAPPC2):​c.*1303dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (83 hom., 163 hem., cov: 5)
  • Exomes 𝑓: 0.041 (0 hom. 0 hem.)
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 0 publications found

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]

TRAPPC2 Gene-Disease associations (from GenCC):

• spondyloepiphyseal dysplasia tarda, X-linked

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• spondyloepiphyseal dysplasia tarda

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011658.4. 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
	TRAPPC2	NM_001011658.4	MANE Select	c.*1303dupT		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*1303dupT		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*1303dupT		3_prime_UTR	Exon 5 of 5	NP_055378.1	P0DI81-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC2	ENST00000380579.6	TSL:1 MANE Select	c.*1303dupT		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*1303dupT		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*1303dupT		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 2219 AN: 68815 Hom.: 84 Cov.: 5

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00329

Gnomad MID AF: 0.00741

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.0204

GnomAD4 exome AF: 0.0407 AC: 5 AN: 123 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 93

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 5

South Asian (SAS) AF: 0.00 AC: 0 AN: 5

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0412 AC: 4 AN: 97

Other (OTH) AF: 0.00 AC: 0 AN: 5

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00192603), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0322 AC: 2213 AN: 68794 Hom.: 83 Cov.: 5 AF XY: 0.0144 AC XY: 163 AN XY: 11328

African (AFR) AF: 0.108 AC: 1915 AN: 17747

American (AMR) AF: 0.0161 AC: 94 AN: 5822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1840

East Asian (EAS) AF: 0.0167 AC: 38 AN: 2278

South Asian (SAS) AF: 0.00626 AC: 8 AN: 1278

European-Finnish (FIN) AF: 0.00329 AC: 6 AN: 1823

Middle Eastern (MID) AF: 0.00813 AC: 1 AN: 123

European-Non Finnish (NFE) AF: 0.00363 AC: 133 AN: 36590

Other (OTH) AF: 0.0202 AC: 18 AN: 893

Alfa AF: 0.00127 Hom.: 203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs35590746; hg19: chrX-13731222;