4-183691400-G-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.1978G>C(p.Val660Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0954 in 1,556,088 control chromosomes in the GnomAD database, including 7,618 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 584 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7034 hom. )

Consequence

TRAPPC11
NM_021942.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.34

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=0.002197057).

BP6

Variant 4-183691400-G-C is Benign according to our data. Variant chr4-183691400-G-C is described in ClinVar as Benign. ClinVar VariationId is 261443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 link	c.1978G>C	p.Val660Leu	missense_variant	Exon 19 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.1978G>C	p.Val660Leu	missense_variant	Exon 19 of 30	1	NM_021942.6	ENSP00000335371.6		Q7Z392-1

Frequencies

GnomAD3 genomes

AF:

0.0840

AC:

12777

AN:

152096

Hom.:

583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0523

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.0551

Gnomad SAS

AF:

0.0643

Gnomad FIN

AF:

0.0637

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.0845

AC:

20722

AN:

245350

AF XY:

0.0852

show subpopulations

Gnomad AFR exome

AF:

0.0467

Gnomad AMR exome

AF:

0.0849

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.0555

Gnomad FIN exome

AF:

0.0655

Gnomad NFE exome

AF:

0.0940

Gnomad OTH exome

AF:

0.0981

GnomAD4 exome

AF:

0.0966

AC:

135588

AN:

1403874

Hom.:

7034

Cov.:

AF XY:

0.0955

AC XY:

66495

AN XY:

696388

show subpopulations

African (AFR)

AF:

0.0466

AC:

1534

AN:

32902

American (AMR)

AF:

0.0873

AC:

3785

AN:

43362

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4134

AN:

24518

East Asian (EAS)

AF:

0.0653

AC:

2540

AN:

38908

South Asian (SAS)

AF:

0.0672

AC:

5018

AN:

74702

European-Finnish (FIN)

AF:

0.0644

AC:

3271

AN:

50764

Middle Eastern (MID)

AF:

0.0790

AC:

437

AN:

5530

European-Non Finnish (NFE)

AF:

0.102

AC:

109304

AN:

1075830

Other (OTH)

AF:

0.0970

AC:

5565

AN:

57358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5413

10826

16238

21651

27064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4226

8452

12678

16904

21130

<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:

0.0840

AC:

12787

AN:

152214

Hom.:

584

Cov.:

AF XY:

0.0822

AC XY:

6119

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0523

AC:

2172

AN:

41544

American (AMR)

AF:

0.101

AC:

1551

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

589

AN:

3470

East Asian (EAS)

AF:

0.0558

AC:

289

AN:

5182

South Asian (SAS)

AF:

0.0638

AC:

308

AN:

4830

European-Finnish (FIN)

AF:

0.0637

AC:

674

AN:

10588

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6933

AN:

67988

Other (OTH)

AF:

0.100

AC:

212

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

612

1225

1837

2450

3062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0927

Hom.:

556

Bravo

AF:

0.0842

ESP6500AA

AF:

0.0524

AC:

231

ESP6500EA

AF:

0.104

AC:

898

ExAC

AF:

0.0822

AC:

9975

Asia WGS

AF:

0.0620

AC:

216

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

- -

not provided

Benign:2

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

T;.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.98

L;L;.

PhyloP100

4.3

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.92

N;N;N

REVEL

Benign

0.052

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.085

MPC

0.29

ClinPred

0.0030

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.28

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over