rs62357990

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.897C>A(p.Ile299Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 1,611,224 control chromosomes in the GnomAD database, including 3,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I299I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.062 ( 359 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3050 hom. )

Consequence

TRAPPC11
NM_021942.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.67

Publications

10 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=-0.52).

BP6

Variant 4-183679418-C-A is Benign according to our data. Variant chr4-183679418-C-A is described in ClinVar as Benign. ClinVar VariationId is 261455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 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.897C>A	p.Ile299Ile	synonymous	Exon 9 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.897C>A	p.Ile299Ile	synonymous	Exon 9 of 31	NP_951008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.897C>A	p.Ile299Ile	synonymous	Exon 9 of 30	ENSP00000335371.6
TRAPPC11	ENST00000357207.8	TSL:1	c.897C>A	p.Ile299Ile	synonymous	Exon 9 of 31	ENSP00000349738.4
TRAPPC11	ENST00000505676.5	TSL:1	n.163-790C>A		intron	N/A	ENSP00000422915.1

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

9378

AN:

152096

Hom.:

358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0511

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0486

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0733

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0602

GnomAD2 exomes

AF:

0.0578

AC:

14437

AN:

249704

AF XY:

0.0564

show subpopulations

Gnomad AFR exome

AF:

0.0491

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0671

Gnomad EAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0656

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0651

GnomAD4 exome

AF:

0.0610

AC:

89040

AN:

1459010

Hom.:

3050

Cov.:

AF XY:

0.0597

AC XY:

43334

AN XY:

725850

show subpopulations

African (AFR)

AF:

0.0462

AC:

1540

AN:

33366

American (AMR)

AF:

0.0365

AC:

1624

AN:

44458

Ashkenazi Jewish (ASJ)

AF:

0.0692

AC:

1802

AN:

26054

East Asian (EAS)

AF:

0.0872

AC:

3442

AN:

39480

South Asian (SAS)

AF:

0.0179

AC:

1539

AN:

85974

European-Finnish (FIN)

AF:

0.0638

AC:

3399

AN:

53244

Middle Eastern (MID)

AF:

0.0660

AC:

380

AN:

5758

European-Non Finnish (NFE)

AF:

0.0641

AC:

71150

AN:

1110414

Other (OTH)

AF:

0.0691

AC:

4164

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

3732

7464

11195

14927

18659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2640

5280

7920

10560

13200

<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:

0.0616

AC:

9374

AN:

152214

Hom.:

359

Cov.:

AF XY:

0.0614

AC XY:

4571

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0510

AC:

2119

AN:

41522

American (AMR)

AF:

0.0484

AC:

740

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

244

AN:

3470

East Asian (EAS)

AF:

0.129

AC:

670

AN:

5182

South Asian (SAS)

AF:

0.0240

AC:

116

AN:

4826

European-Finnish (FIN)

AF:

0.0733

AC:

776

AN:

10590

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0655

AC:

4458

AN:

68020

Other (OTH)

AF:

0.0596

AC:

126

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

447

894

1342

1789

2236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0568

Hom.:

283

Bravo

AF:

0.0616

Asia WGS

AF:

0.0730

AC:

253

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

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

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.0

(source)

DANN

Benign

0.79

PhyloP100

-1.7

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over