X-13712668-G-C

Variant names:

• chrX-13712668-G-C
• rs7716
• NM_001011658.4:c.*1739C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001011658.4(TRAPPC2):​c.*1739C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (19527 hom., 23170 hem., cov: 23)
  • Exomes 𝑓: 0.83 (1 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC2 NM_001011658.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.654
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-13712668-G-C is Benign according to our data. Variant chrX-13712668-G-C is described in ClinVar as Benign. ClinVar VariationId is 367968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

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.*1739C>G		3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
	TRAPPC2	NM_001128835.3		c.*1739C>G		3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
	TRAPPC2	NM_014563.6		c.*1739C>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.*1739C>G		3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
	TRAPPC2	ENST00000683983.1		c.*1739C>G		3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
	TRAPPC2	ENST00000359680.9	TSL:1	c.*1739C>G		3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 77909 AN: 110495 Hom.: 19527 Cov.: 23

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

African (AFR) AF: 1.00 AC: 1 AN: 1

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) AF: 0.750 AC: 3 AN: 4

Other (OTH) AF: 1.00 AC: 1 AN: 1

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.705 AC: 77964 AN: 110549 Hom.: 19527 Cov.: 23 AF XY: 0.708 AC XY: 23170 AN XY: 32745

African (AFR) AF: 0.794 AC: 24169 AN: 30453

American (AMR) AF: 0.756 AC: 7865 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 1692 AN: 2639

East Asian (EAS) AF: 0.818 AC: 2869 AN: 3507

South Asian (SAS) AF: 0.794 AC: 2070 AN: 2608

European-Finnish (FIN) AF: 0.648 AC: 3754 AN: 5791

Middle Eastern (MID) AF: 0.624 AC: 133 AN: 213

European-Non Finnish (NFE) AF: 0.644 AC: 33966 AN: 52748

Other (OTH) AF: 0.723 AC: 1093 AN: 1512

Alfa AF: 0.446 Hom.: 2089

Bravo AF: 0.718

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Spondyloepiphyseal dysplasia tarda (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.82
DANN	Benign	0.42
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7716; hg19: chrX-13730787;