rs141809461

Variant names:

• chrX-13713178-G-A
• rs141809461
• NM_001011658.4:c.*1229C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001011658.4(TRAPPC2):​c.*1229C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 109,503 control chromosomes in the GnomAD database, including 19 homozygotes. There are 316 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (19 hom., 316 hem., cov: 21)
  • 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.252

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-13713178-G-A is Benign according to our data. Variant chrX-13713178-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 367971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0105 (1146/109503) while in subpopulation SAS AF= 0.0429 (109/2538). AF 95% confidence interval is 0.0364. There are 19 homozygotes in gnomad4. There are 316 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4	c.*1229C>T		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.*1229C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1
TRAPPC2	ENST00000683983	c.*1229C>T		3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1
TRAPPC2	ENST00000359680	c.*1229C>T		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5
TRAPPC2	ENST00000683569	c.*1229C>T		3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1142 AN: 109472 Hom.: 20 Cov.: 21 AF XY: 0.00987 AC XY: 315 AN XY: 31908

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00114

Gnomad EAS AF: 0.0230

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.000182

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.000513

Gnomad OTH AF: 0.0208

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 39 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 13

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0105 AC: 1146 AN: 109503 Hom.: 19 Cov.: 21 AF XY: 0.00989 AC XY: 316 AN XY: 31949

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00114

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.000182

Gnomad4 NFE AF: 0.000513

Gnomad4 OTH AF: 0.0226

Alfa AF: 0.00712 Hom.: 20

Bravo AF: 0.0117

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Spondyloepiphyseal dysplasia tarda Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.084
DANN	Benign	0.31

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: rs141809461; hg19: chrX-13731297;