4-183693964-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/20 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

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type R18
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet
intellectual disability-hyperkinetic movement-truncal ataxia syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
triple-A syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRAPPC11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 261448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021942.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	NM_021942.6	MANE Select	c.2434A>C	p.Thr812Pro	missense	Exon 22 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.2434A>C	p.Thr812Pro	missense	Exon 22 of 31	NP_951008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.2434A>C	p.Thr812Pro	missense	Exon 22 of 30	ENSP00000335371.6
TRAPPC11	ENST00000357207.8	TSL:1	c.2434A>C	p.Thr812Pro	missense	Exon 22 of 31	ENSP00000349738.4
TRAPPC11	ENST00000512476.1	TSL:1	c.1252A>C	p.Thr418Pro	missense	Exon 11 of 19	ENSP00000421004.1

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

GnomAD2 exomes

AF:

0.0811

AC:

20383

AN:

251280

AF XY:

0.0837

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 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

African (AFR)

AF:

0.0170

AC:

570

AN:

33478

American (AMR)

AF:

0.0324

AC:

1451

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0477

AC:

1246

AN:

26130

East Asian (EAS)

AF:

0.0392

AC:

1554

AN:

39688

South Asian (SAS)

AF:

0.0737

AC:

6354

AN:

86238

European-Finnish (FIN)

AF:

0.0984

AC:

5258

AN:

53414

Middle Eastern (MID)

AF:

0.0345

AC:

199

AN:

5768

European-Non Finnish (NFE)

AF:

0.126

AC:

140364

AN:

1111738

Other (OTH)

AF:

0.0908

AC:

5482

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7070

14140

21210

28280

35350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5008

10016

15024

20032

25040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0744

AC:

11327

AN:

152266

Hom.:

572

Cov.:

AF XY:

0.0717

AC XY:

5340

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0211

AC:

876

AN:

41548

American (AMR)

AF:

0.0376

AC:

576

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0476

AC:

165

AN:

3470

East Asian (EAS)

AF:

0.0304

AC:

158

AN:

5192

South Asian (SAS)

AF:

0.0715

AC:

345

AN:

4824

European-Finnish (FIN)

AF:

0.0966

AC:

1023

AN:

10594

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7964

AN:

68018

Other (OTH)

AF:

0.0516

AC:

109

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

521

1042

1562

2083

2604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.101

Hom.:

1294

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.7

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.014

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

0.47

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.59

REVEL

Benign

0.015

Sift

Benign

0.15

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.13

MPC

0.24

ClinPred

0.0017

GERP RS

-1.6

Varity_R

0.060

gMVP

0.55

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over