X-13713450-CAA-CAAAAAAAAA

Variant names:

• chrX-13713450-C-CAAAAAAA
• rs57103709
• NM_001011658.4:c.*950_*956dupTTTTTTT

Variant summary

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

The NM_001011658.4(TRAPPC2):​c.*950_*956dupTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (4376 hom., 4105 hem., cov: 0)
  • Exomes 𝑓: 0.053 (0 hom. 1 hem.)
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.240
• 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: G2P, Labcorp Genetics (formerly Invitae)
• 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 = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4	c.*950_*956dupTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	ENST00000380579.6	NP_001011658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC2	ENST00000380579.6	c.*950_*956dupTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1
TRAPPC2	ENST00000683983.1	c.*950_*956dupTTTTTTT		3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1
TRAPPC2	ENST00000359680.9	c.*950_*956dupTTTTTTT		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5
TRAPPC2	ENST00000683569.1	c.*950_*956dupTTTTTTT		3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 27566 AN: 84111 Hom.: 4380 Cov.: 0

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.254

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.0526 AC: 1 AN: 19 Hom.: 0 Cov.: 0 AF XY: 0.0909 AC XY: 1 AN XY: 11

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 1

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0588 AC: 1 AN: 17

Other (OTH) AF: 0.00 AC: 0 AN: 1

GnomAD4 genome AF: 0.328 AC: 27551 AN: 84086 Hom.: 4376 Cov.: 0 AF XY: 0.251 AC XY: 4105 AN XY: 16328

African (AFR) AF: 0.375 AC: 7660 AN: 20452

American (AMR) AF: 0.228 AC: 1569 AN: 6885

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 729 AN: 2339

East Asian (EAS) AF: 0.334 AC: 854 AN: 2556

South Asian (SAS) AF: 0.228 AC: 340 AN: 1490

European-Finnish (FIN) AF: 0.225 AC: 608 AN: 2700

Middle Eastern (MID) AF: 0.244 AC: 38 AN: 156

European-Non Finnish (NFE) AF: 0.332 AC: 15224 AN: 45847

Other (OTH) AF: 0.327 AC: 346 AN: 1059

Alfa AF: 0.133 Hom.: 392

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Spondyloepiphyseal dysplasia congenita Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57103709; hg19: chrX-13731569;