4-183679448-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021942.6(TRAPPC11):c.927A>G(p.Ala309Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,609,180 control chromosomes in the GnomAD database, including 159,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19006 hom., cov: 33)

Exomes 𝑓: 0.44 ( 140525 hom. )

Consequence

TRAPPC11
NM_021942.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.93

Publications

20 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-183679448-A-G is Benign according to our data. Variant chr4-183679448-A-G is described in ClinVar as Benign. ClinVar VariationId is 261456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 link	c.927A>G	p.Ala309Ala	synonymous_variant	Exon 9 of 30	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TRAPPC11	ENST00000334690.11 link	c.927A>G	p.Ala309Ala	synonymous_variant	Exon 9 of 30	1	NM_021942.6	ENSP00000335371.6
TRAPPC11	ENST00000357207.8 link	c.927A>G	p.Ala309Ala	synonymous_variant	Exon 9 of 31	1		ENSP00000349738.4
TRAPPC11	ENST00000505676.5 link	n.163-760A>G		intron_variant	Intron 2 of 18	1		ENSP00000422915.1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74699

AN:

151936

Hom.:

18967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.457

GnomAD2 exomes

AF:

0.447

AC:

111355

AN:

248950

AF XY:

0.433

show subpopulations

Gnomad AFR exome

AF:

0.621

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.511

Gnomad FIN exome

AF:

0.475

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.435

GnomAD4 exome

AF:

0.435

AC:

634269

AN:

1457126

Hom.:

140525

Cov.:

AF XY:

0.430

AC XY:

311409

AN XY:

724996

show subpopulations

African (AFR)

AF:

0.622

AC:

20723

AN:

33320

American (AMR)

AF:

0.513

AC:

22735

AN:

44296

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

11170

AN:

26012

East Asian (EAS)

AF:

0.510

AC:

20107

AN:

39464

South Asian (SAS)

AF:

0.315

AC:

27037

AN:

85742

European-Finnish (FIN)

AF:

0.473

AC:

25134

AN:

53154

Middle Eastern (MID)

AF:

0.396

AC:

2283

AN:

5760

European-Non Finnish (NFE)

AF:

0.431

AC:

478426

AN:

1109182

Other (OTH)

AF:

0.443

AC:

26654

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

16340

32680

49020

65360

81700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14682

29364

44046

58728

73410

<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:

0.492

AC:

74795

AN:

152054

Hom.:

19006

Cov.:

AF XY:

0.491

AC XY:

36459

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.620

AC:

25736

AN:

41482

American (AMR)

AF:

0.486

AC:

7413

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1467

AN:

3470

East Asian (EAS)

AF:

0.525

AC:

2714

AN:

5168

South Asian (SAS)

AF:

0.328

AC:

1583

AN:

4828

European-Finnish (FIN)

AF:

0.487

AC:

5129

AN:

10542

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.431

AC:

29333

AN:

67988

Other (OTH)

AF:

0.461

AC:

971

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1893

3785

5678

7570

9463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.443

Hom.:

53591

Bravo

AF:

0.499

Asia WGS

AF:

0.458

AC:

1592

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

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.

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: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

-0.90

CADD

Benign

0.33

(source)

DANN

Benign

0.56

PhyloP100

-1.9

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