chr4-183694013-T-C

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.2483T>C(p.Val828Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00962 in 1,613,952 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0098 ( 110 hom. )

Consequence

TRAPPC11
NM_021942.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 8.02

Publications

7 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, 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=0.008762926).

BP6

Variant 4-183694013-T-C is Benign according to our data. Variant chr4-183694013-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00771 (1174/152340) while in subpopulation NFE AF = 0.0107 (729/68034). AF 95% confidence interval is 0.0101. There are 9 homozygotes in GnomAd4. There are 582 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	NM_021942.6	MANE Select	c.2483T>C	p.Val828Ala	missense	Exon 22 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.2483T>C	p.Val828Ala	missense	Exon 22 of 31	NP_951008.1	Q7Z392-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.2483T>C	p.Val828Ala	missense	Exon 22 of 30	ENSP00000335371.6	Q7Z392-1
TRAPPC11	ENST00000357207.8	TSL:1	c.2483T>C	p.Val828Ala	missense	Exon 22 of 31	ENSP00000349738.4	Q7Z392-3
TRAPPC11	ENST00000512476.1	TSL:1	c.1301T>C	p.Val434Ala	missense	Exon 11 of 19	ENSP00000421004.1	D6RHE5

Frequencies

GnomAD3 genomes

AF:

0.00771

AC:

1174

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.00797

AC:

2003

AN:

251238

AF XY:

0.00828

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00518

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00956

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00982

AC:

14349

AN:

1461612

Hom.:

110

Cov.:

AF XY:

0.00991

AC XY:

7204

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

33480

American (AMR)

AF:

0.00543

AC:

243

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00750

AC:

196

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00660

AC:

569

AN:

86246

European-Finnish (FIN)

AF:

0.00859

AC:

459

AN:

53410

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0110

AC:

12183

AN:

1111788

Other (OTH)

AF:

0.00956

AC:

577

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

667

1334

2002

2669

3336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.00771

AC:

1174

AN:

152340

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

582

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00214

AC:

AN:

41582

American (AMR)

AF:

0.00811

AC:

124

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00704

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0115

AC:

122

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0107

AC:

729

AN:

68034

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

122

184

245

306

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:

0.00977

Hom.:

Bravo

AF:

0.00716

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0112

AC:

ExAC

AF:

0.00834

AC:

1013

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0113

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (2)

Autosomal recessive limb-girdle muscular dystrophy type R18 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.4

PhyloP100

8.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.2

REVEL

Benign

0.076

Sift

Uncertain

0.0090

Sift4G

Benign

0.11

Polyphen

0.17

Vest4

0.56

MVP

0.44

MPC

0.31

ClinPred

0.023

GERP RS

5.8

Varity_R

0.077

gMVP

0.48

Mutation Taster

=97/3

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over