rs62617790

Positions:

chr4-183697783-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000334690.11(TRAPPC11):c.2799G>C(p.Gln933His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,842 control chromosomes in the GnomAD database, including 14,189 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1047 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13142 hom. )

Consequence

TRAPPC11
ENST00000334690.11 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.68

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017220974).

BP6

Variant 4-183697783-G-C is Benign according to our data. Variant chr4-183697783-G-C is described in ClinVar as [Benign]. Clinvar id is 261451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183697783-G-C is described in Lovd as [Likely_pathogenic]. Variant chr4-183697783-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 linkuse as main transcript	c.2799G>C	p.Gln933His	missense_variant	25/30	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.2799G>C	p.Gln933His	missense_variant	25/30	1	NM_021942.6	ENSP00000335371	P1	Q7Z392-1
TRAPPC11	ENST00000357207.8 linkuse as main transcript	c.2799G>C	p.Gln933His	missense_variant	25/31	1		ENSP00000349738		Q7Z392-3
TRAPPC11	ENST00000512476.1 linkuse as main transcript	c.1617G>C	p.Gln539His	missense_variant	14/19	1		ENSP00000421004
TRAPPC11	ENST00000505676.5 linkuse as main transcript	c.*913G>C		3_prime_UTR_variant, NMD_transcript_variant	13/19	1		ENSP00000422915

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15921

AN:

152002

Hom.:

1048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0496

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.0780

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.133

AC:

33364

AN:

251266

Hom.:

2674

AF XY:

0.141

AC XY:

19129

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0473

Gnomad AMR exome

AF:

0.0518

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.126

AC:

184724

AN:

1461722

Hom.:

13142

Cov.:

AF XY:

0.131

AC XY:

94910

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0476

Gnomad4 AMR exome

AF:

0.0547

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.270

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.105

AC:

15920

AN:

152120

Hom.:

1047

Cov.:

AF XY:

0.109

AC XY:

8114

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0495

Gnomad4 AMR

AF:

0.0779

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.124

Hom.:

954

Bravo

AF:

0.0966

TwinsUK

AF:

0.112

AC:

417

ALSPAC

AF:

0.113

AC:

435

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.121

AC:

1043

ExAC

AF:

0.137

AC:

16627

Asia WGS

AF:

0.212

AC:

736

AN:

3478

EpiCase

AF:

0.122

EpiControl

AF:

0.127

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive limb-girdle muscular dystrophy type R18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

4.5e-7

P;P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.025

D;D;D

Sift4G

Benign

0.11

T;T;D

Polyphen

1.0

D;D;D

Vest4

0.28

MutPred

0.27

Loss of glycosylation at S930 (P = 0.0279);Loss of glycosylation at S930 (P = 0.0279);.;

MPC

0.17

ClinPred

0.017

GERP RS

4.7

Varity_R

0.21

gMVP

0.51

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