X-13713103-CAAAAAA-CAA

Variant names:

• chrX-13713103-CAAAA-C
• rs35590746
• NM_001011658.4:c.*1300_*1303delTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001011658.4(TRAPPC2):​c.*1300_*1303delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 69,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., 1 hem., cov: 5)
  • Exomes 𝑓: 0.0062 (0 hom. 0 hem.)
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4	c.*1300_*1303delTTTT		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.*1300_*1303delTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1
TRAPPC2	ENST00000683983	c.*1300_*1303delTTTT		3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1
TRAPPC2	ENST00000359680	c.*1300_*1303delTTTT		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5
TRAPPC2	ENST00000683569	c.*1300_*1303delTTTT		3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 1 AN: 68899 Hom.: 0 Cov.: 5 AF XY: 0.0000881 AC XY: 1 AN XY: 11345

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000273

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00621 AC: 1 AN: 161 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000145 AC: 1 AN: 68899 Hom.: 0 Cov.: 5 AF XY: 0.0000881 AC XY: 1 AN XY: 11345

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000273

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35590746; hg19: chrX-13731222;