Genetic Variant TRAPPC2:c.*953_*956dupTTTT (chrX-13713450-C-CAAAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001011658.4(TRAPPC2):c.*953_*956dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., 6 hem., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

TRAPPC2
NM_001011658.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000437 (37/84742) while in subpopulation AFR AF = 0.00165 (34/20657). AF 95% confidence interval is 0.00121. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 37 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC2	NM_001011658.4 link	c.953_956dupTTTT		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.953_956dupTTTT	3_prime_UTR_variant	Exon 6 of 6	1	NM_001011658.4	ENSP00000369953.1	P0DI81-1
TRAPPC2	ENST00000683983.1 link	c.953_956dupTTTT	3_prime_UTR_variant	Exon 6 of 6			ENSP00000507474.1	P0DI81-3
TRAPPC2	ENST00000359680.9 link	c.953_956dupTTTT	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352708.5	P0DI81-1
TRAPPC2	ENST00000683569.1 link	c.953_956dupTTTT	3_prime_UTR_variant	Exon 7 of 7			ENSP00000508155.1	P0DI81-1

Frequencies

GnomAD3 genomes

AF:

0.000437

AC:

AN:

84764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000217

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.000437

AC:

AN:

84742

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

AN XY:

16442

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

20657

American (AMR)

AF:

0.000144

AC:

AN:

6931

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2343

East Asian (EAS)

AF:

0.000391

AC:

AN:

2560

South Asian (SAS)

AF:

0.00

AC:

AN:

1500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

160

European-Non Finnish (NFE)

AF:

0.0000217

AC:

AN:

46153

Other (OTH)

AF:

0.00

AC:

AN:

1074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over