Genetic Variant TRAPPC2:c.*1300_*1303delTTTT (chrX-13713103-CAAAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001011658.4(TRAPPC2):c.*1300_*1303delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 69,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., 1 hem., cov: 5)

Exomes 𝑓: 0.0062 ( 0 hom. 0 hem. )

Consequence

TRAPPC2
NM_001011658.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.121

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1300_1303delTTTT	3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
TRAPPC2	NM_001128835.3		c.1300_1303delTTTT	3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
TRAPPC2	NM_014563.6		c.1300_1303delTTTT	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.1300_1303delTTTT	3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
TRAPPC2	ENST00000683983.1		c.1300_1303delTTTT	3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
TRAPPC2	ENST00000359680.9	TSL:1	c.1300_1303delTTTT	3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes

AF:

0.0000145

AC:

AN:

68899

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000273

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00621

AC:

AN:

161

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131

show subpopulations

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

African (AFR)

AF:

0.200

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:

126

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000145

AC:

AN:

68899

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

11345

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17768

American (AMR)

AF:

0.00

AC:

AN:

5822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1840

East Asian (EAS)

AF:

0.00

AC:

AN:

2291

South Asian (SAS)

AF:

0.00

AC:

AN:

1289

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1829

Middle Eastern (MID)

AF:

0.00

AC:

AN:

135

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

36639

Other (OTH)

AF:

0.00

AC:

AN:

884

Age Distribution

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.:

203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.12

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

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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