X-13713450-CAA-CAAAAAA

Variant names:

• chrX-13713450-C-CAAAA
• rs57103709
• NM_001011658.4:c.*953_*956dupTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001011658.4(TRAPPC2):​c.*953_*956dupTTTT 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 0.00044 (0 hom., 6 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: 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000437 (37/84742) while in subpopulation AFR AF = 0.00165 (34/20657). AF 95% confidence interval is 0.00121. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 37 XL,AD gene.

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.*953_*956dupTTTT		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*953_*956dupTTTT		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*953_*956dupTTTT		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.*953_*956dupTTTT		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*953_*956dupTTTT		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*953_*956dupTTTT		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.000437 AC: 37 AN: 84764 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000217

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 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: 0.000437 AC: 37 AN: 84742 Hom.: 0 Cov.: 0 AF XY: 0.000365 AC XY: 6 AN XY: 16442

African (AFR) AF: 0.00165 AC: 34 AN: 20657

American (AMR) AF: 0.000144 AC: 1 AN: 6931

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

East Asian (EAS) AF: 0.000391 AC: 1 AN: 2560

South Asian (SAS) AF: 0.00 AC: 0 AN: 1500

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: 0.0000217 AC: 1 AN: 46153

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

Alfa AF: 0.00 Hom.: 392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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;