NM_001011658.4:c.*1052T>C

Variant names:

• chrX-13713355-A-G
• rs5979952
• NM_001011658.4:c.*1052T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001011658.4(TRAPPC2):​c.*1052T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (3360 hom., 6592 hem., cov: 19)
  • Exomes 𝑓: 0.27 (8 hom. 25 hem.)
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.240
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant X-13713355-A-G is Benign according to our data. Variant chrX-13713355-A-G is described in ClinVar as Benign. ClinVar VariationId is 367973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 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.*1052T>C		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*1052T>C		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*1052T>C		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.*1052T>C		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*1052T>C		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*1052T>C		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 29305 AN: 102617 Hom.: 3363 Cov.: 19

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.272 AC: 52 AN: 191 Hom.: 8 Cov.: 0 AF XY: 0.243 AC XY: 25 AN XY: 103

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

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

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 9

South Asian (SAS) AF: 0.00 AC: 0 AN: 7

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.316 AC: 50 AN: 158

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.285 AC: 29300 AN: 102644 Hom.: 3360 Cov.: 19 AF XY: 0.248 AC XY: 6592 AN XY: 26598

African (AFR) AF: 0.269 AC: 7522 AN: 27917

American (AMR) AF: 0.204 AC: 1922 AN: 9422

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 770 AN: 2543

East Asian (EAS) AF: 0.161 AC: 512 AN: 3174

South Asian (SAS) AF: 0.217 AC: 478 AN: 2201

European-Finnish (FIN) AF: 0.293 AC: 1355 AN: 4620

Middle Eastern (MID) AF: 0.270 AC: 51 AN: 189

European-Non Finnish (NFE) AF: 0.318 AC: 16099 AN: 50560

Other (OTH) AF: 0.294 AC: 409 AN: 1392

Alfa AF: 0.158 Hom.: 727

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Spondyloepiphyseal dysplasia tarda (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.12
PhyloP100		0.24
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: rs5979952; hg19: chrX-13731474;