Variant chr4-183693057-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021942.6(TRAPPC11):c.2147C>A(p.Ala716Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TRAPPC11
NM_021942.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.59

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 linkuse as main transcript	c.2147C>A	p.Ala716Asp	missense_variant	20/30	ENST00000334690.11	NP_068761.4	Q7Z392-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11 linkuse as main transcript	c.2147C>A	p.Ala716Asp	missense_variant	20/30	1	NM_021942.6	ENSP00000335371.6		Q7Z392-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251116

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461410

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.2147C>A (p.A716D) alteration is located in exon 20 (coding exon 19) of the TRAPPC11 gene. This alteration results from a C to A substitution at nucleotide position 2147, causing the alanine (A) at amino acid position 716 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Autosomal recessive limb-girdle muscular dystrophy type R18

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 21, 2023

This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 716 of the TRAPPC11 protein (p.Ala716Asp). This variant is present in population databases (rs143990563, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TRAPPC11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1378704). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TRAPPC11 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;.;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.0074

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.12

T;T;D

Sift4G

Benign

0.44

T;T;T

Polyphen

0.80

P;D;D

Vest4

0.77

MutPred

0.40

Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);.;

MVP

0.30

MPC

0.80

ClinPred

0.36

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.24

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over