Genetic Variant NM_021942.6:c.1978G>A (chr4-183691400-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021942.6(TRAPPC11):c.1978G>A(p.Val660Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000783 in 1,404,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V660L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

TRAPPC11
NM_021942.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.34

Publications

17 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07321912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 link	c.1978G>A	p.Val660Ile	missense_variant	Exon 19 of 30	ENST00000334690.11	NP_068761.4	Q7Z392-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11 link	c.1978G>A	p.Val660Ile	missense_variant	Exon 19 of 30	1	NM_021942.6	ENSP00000335371.6		Q7Z392-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000815

AC:

AN:

245350

AF XY:

0.00000754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000783

AC:

AN:

1404720

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

696856

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32914

American (AMR)

AF:

0.00

AC:

AN:

43422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24558

East Asian (EAS)

AF:

0.00

AC:

AN:

38922

South Asian (SAS)

AF:

0.00

AC:

AN:

74802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.00000929

AC:

AN:

1076396

Other (OTH)

AF:

0.00

AC:

AN:

57394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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.:

Alfa

AF:

0.00

Hom.:

556

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.021

T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0030

MetaRNN

Benign

0.073

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;.

PhyloP100

4.3

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.77

T;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.11

MutPred

0.30

Loss of MoRF binding (P = 0.1205);Loss of MoRF binding (P = 0.1205);.;

MVP

0.52

MPC

0.25

ClinPred

0.50

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.12

Mutation Taster

=97/3

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over