X-13713450-CAA-CAAAAAAAAAAAAAAAAA

Variant names:

• chrX-13713450-C-CAAAAAAAAAAAAAAA
• rs57103709
• NM_001011658.4:c.*956_*957insTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001011658.4(TRAPPC2):​c.*956_*957insTTTTTTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4	c.*956_*957insTTTTTTTTTTTTTTT		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.*956_*957insTTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1
TRAPPC2	ENST00000683983.1	c.*956_*957insTTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1
TRAPPC2	ENST00000359680.9	c.*956_*957insTTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5
TRAPPC2	ENST00000683569.1	c.*956_*957insTTTTTTTTTTTTTTT		3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1

Frequencies

GnomAD3 genomes AF: 0.0000354 AC: 3 AN: 84745 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000433

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

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) AF: 0.00 AC: 0 AN: 1

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: 0.00 AC: 0 AN: 19

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

GnomAD4 genome AF: 0.0000354 AC: 3 AN: 84721 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16441

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

African (AFR) AF: 0.0000484 AC: 1 AN: 20649

American (AMR) AF: 0.00 AC: 0 AN: 6926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2343

East Asian (EAS) AF: 0.00 AC: 0 AN: 2560

South Asian (SAS) AF: 0.00 AC: 0 AN: 1498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 160

European-Non Finnish (NFE) AF: 0.0000433 AC: 2 AN: 46147

Other (OTH) AF: 0.00 AC: 0 AN: 1074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000728 Hom.: 392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24

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;