dbSNP rs4862234: TRAPPC11:p.Thr790Thr (chr4-183693721-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_021942.6(TRAPPC11):c.2370C>T(p.Thr790Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,613,170 control chromosomes in the GnomAD database, including 44,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4767 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39679 hom. )

Consequence

TRAPPC11
NM_021942.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.74

Variant links:

Genes affected

TRAPPC11 (HGNC:25751): (trafficking protein particle complex subunit 11) The protein encoded by this gene is a subunit of the TRAPP (transport protein particle) tethering complex, which functions in intracellular vesicle trafficking. This subunit is involved in early stage endoplasmic reticulum-to-Golgi vesicle transport. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2013]

TRAPPC11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 4-183693721-C-T is Benign according to our data. Variant chr4-183693721-C-T is described in ClinVar as [Benign]. Clinvar id is 261446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183693721-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 link	c.2370C>T	p.Thr790Thr	synonymous_variant	Exon 21 of 30	ENST00000334690.11	NP_068761.4	Q7Z392-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11 link	c.2370C>T	p.Thr790Thr	synonymous_variant	Exon 21 of 30	1	NM_021942.6	ENSP00000335371.6		Q7Z392-1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37266

AN:

151906

Hom.:

4761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.217

AC:

54442

AN:

250474

Hom.:

6229

AF XY:

0.213

AC XY:

28812

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.229

AC:

335051

AN:

1461146

Hom.:

39679

Cov.:

AF XY:

0.226

AC XY:

164553

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.245

AC:

37319

AN:

152024

Hom.:

4767

Cov.:

AF XY:

0.243

AC XY:

18057

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.231

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.229

Hom.:

5513

Bravo

AF:

0.243

Asia WGS

AF:

0.160

AC:

555

AN:

3478

EpiCase

AF:

0.219

EpiControl

AF:

0.218

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 24, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive limb-girdle muscular dystrophy type R18

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

0.24

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over