NM_001011658.4:c.*2108_*2109dupTG

Variant names:

• chrX-13712297-T-TCA
• rs199924403
• NM_001011658.4:c.*2108_*2109dupTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001011658.4(TRAPPC2):​c.*2108_*2109dupTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 112,328 control chromosomes in the GnomAD database, including 56 homozygotes. There are 556 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (56 hom., 556 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.238

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-13712297-T-TCA is Benign according to our data. Variant chrX-13712297-T-TCA is described in ClinVar as [Benign]. Clinvar id is 367964.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.067 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4	c.*2108_*2109dupTG		3_prime_UTR_variant	Exon 6 of 6	ENST00000380579.6	NP_001011658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC2	ENST00000380579	c.*2108_*2109dupTG		3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1
TRAPPC2	ENST00000683983	c.*2108_*2109dupTG		3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1
TRAPPC2	ENST00000359680	c.*2108_*2109dupTG		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5
TRAPPC2	ENST00000683569	c.*2108_*2109dupTG		3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 2265 AN: 112275 Hom.: 56 Cov.: 22 AF XY: 0.0159 AC XY: 548 AN XY: 34435

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00804

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0159

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0203 AC: 2276 AN: 112328 Hom.: 56 Cov.: 22 AF XY: 0.0161 AC XY: 556 AN XY: 34498

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.00803

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.0142 Hom.: 43

Bravo AF: 0.0233

Asia WGS AF: 0.00438 AC: 11 AN: 2519

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spondyloepiphyseal dysplasia congenita Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199924403; hg19: chrX-13730416;