Genetic Variant TRAPPC2:c.*1302_*1303delTT (chrX-13713103-CAA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001011658.4(TRAPPC2):c.*1302_*1303delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 0 hem., cov: 5)

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: 0.108

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

TRAPPC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAPPC2	NM_001011658.4	MANE Select	c.1302_1303delTT	3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
TRAPPC2	NM_001128835.3		c.1302_1303delTT	3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
TRAPPC2	NM_014563.6		c.1302_1303delTT	3_prime_UTR	Exon 5 of 5	NP_055378.1	P0DI81-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAPPC2	ENST00000380579.6	TSL:1 MANE Select	c.1302_1303delTT	3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
TRAPPC2	ENST00000683983.1		c.1302_1303delTT	3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
TRAPPC2	ENST00000359680.9	TSL:1	c.1302_1303delTT	3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes

AF:

0.000232

AC:

AN:

68885

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000563

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000859

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000436

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00110

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

143

Hom.:

AF XY:

0.00

AC XY:

AN XY:

113

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

109

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.000232

AC:

AN:

68864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11336

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000562

AC:

AN:

17779

American (AMR)

AF:

0.000858

AC:

AN:

5825

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1840

East Asian (EAS)

AF:

0.000439

AC:

AN:

2280

South Asian (SAS)

AF:

0.00

AC:

AN:

1278

European-Finnish (FIN)

AF:

0.00110

AC:

AN:

1826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

123

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

36616

Other (OTH)

AF:

0.00

AC:

AN:

895

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000166036), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.394

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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.:

203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-13713103-CAAAAAA-CAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over