NM_001011658.4:c.*989G>T

Variant names:

• chrX-13713418-C-A
• rs1449359101
• NM_001011658.4:c.*989G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001011658.4(TRAPPC2):​c.*989G>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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.931
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.*989G>T		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*989G>T		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*989G>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.*989G>T		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*989G>T		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*989G>T		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.000467 AC: 41 AN: 87743 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000678

Gnomad AMI AF: 0.00172

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.000438

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.000592

Gnomad FIN AF: 0.000518

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000263

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 3

South Asian (SAS) AC: 0 AN: 0

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 27

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000467 AC: 41 AN: 87772 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 20838

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

African (AFR) AF: 0.000676 AC: 15 AN: 22177

American (AMR) AF: 0.000785 AC: 6 AN: 7641

Ashkenazi Jewish (ASJ) AF: 0.000438 AC: 1 AN: 2284

East Asian (EAS) AF: 0.00111 AC: 3 AN: 2704

South Asian (SAS) AF: 0.000595 AC: 1 AN: 1682

European-Finnish (FIN) AF: 0.000518 AC: 2 AN: 3863

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 125

European-Non Finnish (NFE) AF: 0.000263 AC: 12 AN: 45608

Other (OTH) AF: 0.00 AC: 0 AN: 1108

⚠️ 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: 0.00251 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	-0.90
CADD	Benign	1.1
DANN	Benign	0.73
PhyloP100		-0.93

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: rs1449359101; hg19: chrX-13731537;