X-13713103-CAAAAAA-CAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001011658.4(TRAPPC2):​c.*1303delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (2617 hom., 2731 hem., cov: 5)
  • Exomes 𝑓: 0.071 (0 hom. 0 hem.)
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant X-13713103-CA-C is Benign according to our data. Variant chrX-13713103-CA-C is described in ClinVar as Benign. ClinVar VariationId is 367970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.467 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.*1303delT		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*1303delT		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*1303delT		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.*1303delT		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*1303delT		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*1303delT		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 21487 AN: 68727 Hom.: 2612 Cov.: 5

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.0714 AC: 7 AN: 98 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0875 AC: 7 AN: 80

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.313 AC: 21486 AN: 68704 Hom.: 2617 Cov.: 5 AF XY: 0.242 AC XY: 2731 AN XY: 11274

African (AFR) AF: 0.286 AC: 5070 AN: 17738

American (AMR) AF: 0.482 AC: 2800 AN: 5808

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 553 AN: 1834

East Asian (EAS) AF: 0.459 AC: 1042 AN: 2270

South Asian (SAS) AF: 0.461 AC: 587 AN: 1273

European-Finnish (FIN) AF: 0.248 AC: 453 AN: 1828

Middle Eastern (MID) AF: 0.366 AC: 45 AN: 123

European-Non Finnish (NFE) AF: 0.288 AC: 10538 AN: 36536

Other (OTH) AF: 0.339 AC: 303 AN: 894

Alfa AF: 0.0620 Hom.: 203

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spondyloepiphyseal dysplasia congenita (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=99/1	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;