NM_001011658.4:c.*1050C>T

Variant names:

• chrX-13713357-G-A
• rs184686872
• NM_001011658.4:c.*1050C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001011658.4(TRAPPC2):​c.*1050C>T 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., 36 hem., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.252
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant X-13713357-G-A is Benign according to our data. Variant chrX-13713357-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 367974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000953 (101/105947) while in subpopulation SAS AF = 0.0175 (41/2346). AF 95% confidence interval is 0.0132. There are 0 homozygotes in GnomAd4. There are 36 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.
• BS2: High AC in GnomAd4 at 101 AD,XL 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.*1050C>T		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*1050C>T		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*1050C>T		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.*1050C>T		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*1050C>T		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*1050C>T		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.000963 AC: 102 AN: 105912 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000772

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 186 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 98

African (AFR) AF: 0.00 AC: 0 AN: 3

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: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 154

Other (OTH) AF: 0.00 AC: 0 AN: 9

GnomAD4 genome AF: 0.000953 AC: 101 AN: 105947 Hom.: 0 Cov.: 20 AF XY: 0.00124 AC XY: 36 AN XY: 29113

African (AFR) AF: 0.00 AC: 0 AN: 28656

American (AMR) AF: 0.000102 AC: 1 AN: 9840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2606

East Asian (EAS) AF: 0.0163 AC: 55 AN: 3375

South Asian (SAS) AF: 0.0175 AC: 41 AN: 2346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5027

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000772 AC: 4 AN: 51788

Other (OTH) AF: 0.00 AC: 0 AN: 1436

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000861

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

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: rs184686872; hg19: chrX-13731476;