dbSNP rs62358032: TRAPPC11:p.Thr812Pro (chr4-183693964-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021942.6(TRAPPC11):c.2434A>C(p.Thr812Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,613,816 control chromosomes in the GnomAD database, including 10,653 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 572 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10081 hom. )

Consequence

TRAPPC11
NM_021942.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.465

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014404655).

BP6

Variant 4-183693964-A-C is Benign according to our data. Variant chr4-183693964-A-C is described in ClinVar as [Benign]. Clinvar id is 261448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183693964-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 link	c.2434A>C	p.Thr812Pro	missense_variant	Exon 22 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.2434A>C	p.Thr812Pro	missense_variant	Exon 22 of 30	1	NM_021942.6	ENSP00000335371.6		Q7Z392-1

Frequencies

GnomAD3 genomes

AF:

0.0744

AC:

11324

AN:

152148

Hom.:

573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.0304

Gnomad SAS

AF:

0.0713

Gnomad FIN

AF:

0.0966

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0511

GnomAD3 exomes

AF:

0.0811

AC:

20383

AN:

251280

Hom.:

1098

AF XY:

0.0837

AC XY:

11360

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.0322

Gnomad ASJ exome

AF:

0.0469

Gnomad EAS exome

AF:

0.0268

Gnomad SAS exome

AF:

0.0748

Gnomad FIN exome

AF:

0.0958

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.0812

GnomAD4 exome

AF:

0.111

AC:

162478

AN:

1461550

Hom.:

10081

Cov.:

AF XY:

0.110

AC XY:

79923

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.0477

Gnomad4 EAS exome

AF:

0.0392

Gnomad4 SAS exome

AF:

0.0737

Gnomad4 FIN exome

AF:

0.0984

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.0908

GnomAD4 genome

AF:

0.0744

AC:

11327

AN:

152266

Hom.:

572

Cov.:

AF XY:

0.0717

AC XY:

5340

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.0376

Gnomad4 ASJ

AF:

0.0476

Gnomad4 EAS

AF:

0.0304

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.0966

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.0516

Alfa

AF:

0.106

Hom.:

743

Bravo

AF:

0.0672

TwinsUK

AF:

0.132

AC:

489

ALSPAC

AF:

0.128

AC:

493

ESP6500AA

AF:

0.0227

AC:

100

ESP6500EA

AF:

0.116

AC:

997

ExAC

AF:

0.0828

AC:

10056

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

EpiCase

AF:

0.104

EpiControl

AF:

0.101

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type R18

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.7

DANN

Benign

0.95

DEOGEN2

Benign

0.014

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.59

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.13

MPC

0.24

ClinPred

0.0017

GERP RS

-1.6

Varity_R

0.060

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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