rs114471872

Positions:

chr4-183693991-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021942.6(TRAPPC11):c.2461G>A(p.Ala821Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000739 in 1,614,036 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 4 hom. )

Consequence

TRAPPC11
NM_021942.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007376641).

BP6

Variant 4-183693991-G-A is Benign according to our data. Variant chr4-183693991-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183693991-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 linkuse as main transcript	c.2461G>A	p.Ala821Thr	missense_variant	22/30	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11 linkuse as main transcript	c.2461G>A	p.Ala821Thr	missense_variant	22/30	1	NM_021942.6	ENSP00000335371	P1	Q7Z392-1
TRAPPC11	ENST00000357207.8 linkuse as main transcript	c.2461G>A	p.Ala821Thr	missense_variant	22/31	1		ENSP00000349738		Q7Z392-3
TRAPPC11	ENST00000512476.1 linkuse as main transcript	c.1279G>A	p.Ala427Thr	missense_variant	11/19	1		ENSP00000421004
TRAPPC11	ENST00000505676.5 linkuse as main transcript	c.*575G>A		3_prime_UTR_variant, NMD_transcript_variant	10/19	1		ENSP00000422915

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

624

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000883

AC:

222

AN:

251274

Hom.:

AF XY:

0.000611

AC XY:

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000389

AC:

568

AN:

1461736

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

241

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.00410

AC:

624

AN:

152300

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

284

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000731

Hom.:

Bravo

AF:

0.00461

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00101

AC:

123

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 28, 2016

- -

TRAPPC11-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 23, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2021

- -

Autosomal recessive limb-girdle muscular dystrophy type R18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.030

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.19

B;P;D

Vest4

0.55

MVP

0.44

MPC

0.54

ClinPred

0.038

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.45

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

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