rs886041053

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate

The NM_021942.6(TRAPPC11):c.1893+3A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000616 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TRAPPC11
NM_021942.6 splice_region, intron

Scores

Splicing: ADA: 0.9974

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 6.97

Publications

3 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: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

PP5

Variant 4-183686751-A-G is Pathogenic according to our data. Variant chr4-183686751-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 268055.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 link	c.1893+3A>G		splice_region_variant, intron_variant	Intron 18 of 29	ENST00000334690.11	NP_068761.4	Q7Z392-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAPPC11	ENST00000334690.11 link	c.1893+3A>G	splice_region_variant, intron_variant	Intron 18 of 29	1	NM_021942.6	ENSP00000335371.6	Q7Z392-1
TRAPPC11	ENST00000357207.8 link	c.1893+3A>G	splice_region_variant, intron_variant	Intron 18 of 30	1		ENSP00000349738.4	Q7Z392-3
TRAPPC11	ENST00000512476.1 link	c.711+3A>G	splice_region_variant, intron_variant	Intron 7 of 18	1		ENSP00000421004.1	D6RHE5
TRAPPC11	ENST00000505676.5 link	n.*7+3A>G	splice_region_variant, intron_variant	Intron 6 of 18	1		ENSP00000422915.1	D6R9T9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111828

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type R18

Pathogenic:2

Mar 05, 2020

Revvity Omics, Revvity

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 25, 2018

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

7.0

Mutation Taster

=6/94

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.79

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.20

Position offset: -3

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over