Genetic Variant NM_001011658.4:c.*950_*956dupTTTTTTT (chrX-13713450-C-CAAAAAAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001011658.4(TRAPPC2):c.*950_*956dupTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.33 ( 4376 hom., 4105 hem., cov: 0)

Exomes 𝑓: 0.053 ( 0 hom. 1 hem. )

Consequence

TRAPPC2
NM_001011658.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.240

Publications

0 publications found

Variant links:

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: G2P, Labcorp Genetics (formerly Invitae)
spondyloepiphyseal dysplasia tarda
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRAPPC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4 link	c.950_956dupTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	ENST00000380579.6	NP_001011658.1	P0DI81-1P0DI82Q6IBE5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAPPC2	ENST00000380579.6 link	c.950_956dupTTTTTTT	3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1	P0DI81-1
TRAPPC2	ENST00000683983.1 link	c.950_956dupTTTTTTT	3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1	P0DI81-3
TRAPPC2	ENST00000359680.9 link	c.950_956dupTTTTTTT	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5	P0DI81-1
TRAPPC2	ENST00000683569.1 link	c.950_956dupTTTTTTT	3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1	P0DI81-1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

27566

AN:

84111

Hom.:

4380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.254

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.0526

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0909

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0588

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.328

AC:

27551

AN:

84086

Hom.:

4376

Cov.:

AF XY:

0.251

AC XY:

4105

AN XY:

16328

show subpopulations

African (AFR)

AF:

0.375

AC:

7660

AN:

20452

American (AMR)

AF:

0.228

AC:

1569

AN:

6885

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

729

AN:

2339

East Asian (EAS)

AF:

0.334

AC:

854

AN:

2556

South Asian (SAS)

AF:

0.228

AC:

340

AN:

1490

European-Finnish (FIN)

AF:

0.225

AC:

608

AN:

2700

Middle Eastern (MID)

AF:

0.244

AC:

AN:

156

European-Non Finnish (NFE)

AF:

0.332

AC:

15224

AN:

45847

Other (OTH)

AF:

0.327

AC:

346

AN:

1059

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

527

1054

1581

2108

2635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

392

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Spondyloepiphyseal dysplasia congenita

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_001011658.4:c.950_956dupTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over