X-13713450-CAA-CAAAAAAAAAA

Variant names:

• chrX-13713450-C-CAAAAAAAA
• rs57103709
• NM_001011658.4:c.*956_*957insTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001011658.4(TRAPPC2):​c.*956_*957insTTTTTTTT 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 0.26 (3068 hom., 2767 hem., cov: 0)
  • Exomes 𝑓: 0.19 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.240

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-13713450-C-CAAAAAAAA is Benign according to our data. Variant chrX-13713450-C-CAAAAAAAA is described in ClinVar as [Benign]. Clinvar id is 367978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.188 (3/16) while in subpopulation NFE AF= 0.143 (2/14). AF 95% confidence interval is 0.0254. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4	c.*956_*957insTTTTTTTT		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.*956_*957insTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1
TRAPPC2	ENST00000683983	c.*956_*957insTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1
TRAPPC2	ENST00000359680	c.*956_*957insTTTTTTTT		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5
TRAPPC2	ENST00000683569	c.*956_*957insTTTTTTTT		3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 21793 AN: 83941 Hom.: 3068 Cov.: 0 AF XY: 0.170 AC XY: 2765 AN XY: 16311 FAILED QC

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.243

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.260 AC: 21786 AN: 83917 Hom.: 3068 Cov.: 0 AF XY: 0.170 AC XY: 2767 AN XY: 16313

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.252

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

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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: rs57103709; hg19: chrX-13731569;