4-183679344-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021942.6(TRAPPC11):c.832-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,558,362 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 24 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 21 hom. )

Consequence

TRAPPC11
NM_021942.6 intron

Scores

Splicing: ADA: 0.0001246

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.401

Publications

1 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 (BayesDel_noAF=-0.8).

BP6

Variant 4-183679344-A-G is Benign according to our data. Variant chr4-183679344-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 448701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00893 (1359/152130) while in subpopulation AFR AF = 0.0311 (1292/41512). AF 95% confidence interval is 0.0297. There are 24 homozygotes in GnomAd4. There are 641 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

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.832-9A>G		intron	N/A	NP_068761.4
	TRAPPC11	NM_199053.3		c.832-9A>G		intron	N/A	NP_951008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.832-9A>G	intron	N/A	ENSP00000335371.6
TRAPPC11	ENST00000357207.8	TSL:1	c.832-9A>G	intron	N/A	ENSP00000349738.4
TRAPPC11	ENST00000505676.5	TSL:1	n.163-864A>G	intron	N/A	ENSP00000422915.1

Frequencies

GnomAD3 genomes

AF:

0.00889

AC:

1351

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0310

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.00243

AC:

518

AN:

213072

AF XY:

0.00189

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000582

Gnomad OTH exome

AF:

0.000822

GnomAD4 exome

AF:

0.000884

AC:

1243

AN:

1406232

Hom.:

Cov.:

AF XY:

0.000771

AC XY:

537

AN XY:

696396

show subpopulations

African (AFR)

AF:

0.0334

AC:

1025

AN:

30710

American (AMR)

AF:

0.00150

AC:

AN:

32716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24130

East Asian (EAS)

AF:

0.00

AC:

AN:

38132

South Asian (SAS)

AF:

0.0000524

AC:

AN:

76402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52274

Middle Eastern (MID)

AF:

0.000903

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.0000358

AC:

AN:

1088282

Other (OTH)

AF:

0.00208

AC:

121

AN:

58046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00893

AC:

1359

AN:

152130

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

641

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0311

AC:

1292

AN:

41512

American (AMR)

AF:

0.00301

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67980

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00252

Hom.:

Bravo

AF:

0.00972

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 15, 2020

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Dec 03, 2020

GeneDx

Significance:Likely 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

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.5

(source)

DANN

Benign

0.50

PhyloP100

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0

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

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