chrX-13712444-T-C

Variant names:

• chrX-13712444-T-C
• rs147081718
• NM_001011658.4:c.*1963A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001011658.4(TRAPPC2):​c.*1963A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 112,388 control chromosomes in the GnomAD database, including 18 homozygotes. There are 361 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (18 hom., 361 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP6: Variant X-13712444-T-C is Benign according to our data. Variant chrX-13712444-T-C is described in ClinVar as Benign. ClinVar VariationId is 914500.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1398/112388) while in subpopulation AFR AF = 0.0429 (1328/30921). AF 95% confidence interval is 0.041. There are 18 homozygotes in GnomAd4. There are 361 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1398 XL,AD gene.

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.*1963A>G		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*1963A>G		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*1963A>G		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.*1963A>G		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*1963A>G		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*1963A>G		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1393 AN: 112335 Hom.: 18 Cov.: 23

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00443

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000225

Gnomad OTH AF: 0.00662

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0124 AC: 1398 AN: 112388 Hom.: 18 Cov.: 23 AF XY: 0.0104 AC XY: 361 AN XY: 34558

African (AFR) AF: 0.0429 AC: 1328 AN: 30921

American (AMR) AF: 0.00442 AC: 47 AN: 10633

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3601

South Asian (SAS) AF: 0.00 AC: 0 AN: 2719

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6122

Middle Eastern (MID) AF: 0.00457 AC: 1 AN: 219

European-Non Finnish (NFE) AF: 0.000225 AC: 12 AN: 53310

Other (OTH) AF: 0.00654 AC: 10 AN: 1529

Alfa AF: 0.00833 Hom.: 24

Bravo AF: 0.0141

ClinVar

ClinVar submissions

Significance: Benign

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	-0.88
CADD	Benign	7.9
DANN	Benign	0.57
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: 49

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

Other links and lift over

dbSNP: rs147081718; hg19: chrX-13730563;