dbSNP rs1165831875: TRAPPC2:c.*1287G>T (chrX-13713120-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001011658.4(TRAPPC2):c.*1287G>T 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 19)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

TRAPPC2
NM_001011658.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.85

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BS2

High AC in GnomAd4 at 6 XL,AD gene.

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.*1287G>T	3_prime_UTR	Exon 6 of 6	NP_001011658.1	P0DI81-1
TRAPPC2	NM_001128835.3		c.*1287G>T	3_prime_UTR	Exon 6 of 6	NP_001122307.2	P0DI81-3
TRAPPC2	NM_014563.6		c.*1287G>T	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.*1287G>T	3_prime_UTR	Exon 6 of 6	ENSP00000369953.1	P0DI81-1
TRAPPC2	ENST00000683983.1		c.*1287G>T	3_prime_UTR	Exon 6 of 6	ENSP00000507474.1	P0DI81-3
TRAPPC2	ENST00000359680.9	TSL:1	c.*1287G>T	3_prime_UTR	Exon 5 of 5	ENSP00000352708.5	P0DI81-1

Frequencies

GnomAD3 genomes

AF:

0.0000635

AC:

AN:

94486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000825

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000329

Gnomad SAS

AF:

0.000490

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000419

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

183

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

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)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

160

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0000635

AC:

AN:

94500

Hom.:

Cov.:

AF XY:

0.0000838

AC XY:

AN XY:

23866

show subpopulations

African (AFR)

AF:

0.0000824

AC:

AN:

24279

American (AMR)

AF:

0.00

AC:

AN:

8879

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2393

East Asian (EAS)

AF:

0.000331

AC:

AN:

3022

South Asian (SAS)

AF:

0.000495

AC:

AN:

2021

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

161

European-Non Finnish (NFE)

AF:

0.0000419

AC:

AN:

47719

Other (OTH)

AF:

0.00

AC:

AN:

1259

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Spondyloepiphyseal dysplasia tarda (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

9.0

(source)

DANN

Benign

0.41

PhyloP100

-1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -20

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