rs79804817

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000334690.11(TRAPPC11):c.3019G>A(p.Val1007Met) variant causes a missense change. The variant allele was found at a frequency of 0.00168 in 1,598,108 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 51 hom. )

Consequence

TRAPPC11
ENST00000334690.11 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.22

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=0.0064311624).

BP6

Variant 4-183705034-G-A is Benign according to our data. Variant chr4-183705034-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183705034-G-A is described in Lovd as [Benign]. Variant chr4-183705034-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0021 (320/152236) while in subpopulation EAS AF= 0.0424 (219/5168). AF 95% confidence interval is 0.0378. There are 6 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 linkuse as main transcript	c.3019G>A	p.Val1007Met	missense_variant	27/30	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.3019G>A	p.Val1007Met	missense_variant	27/30	1	NM_021942.6	ENSP00000335371	P1	Q7Z392-1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0423

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00427

AC:

1073

AN:

251382

Hom.:

AF XY:

0.00378

AC XY:

513

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0494

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00163

AC:

2361

AN:

1445872

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1174

AN XY:

719436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00234

Gnomad4 EAS exome

AF:

0.0455

Gnomad4 SAS exome

AF:

0.000975

Gnomad4 FIN exome

AF:

0.00310

Gnomad4 NFE exome

AF:

0.0000972

Gnomad4 OTH exome

AF:

0.00231

GnomAD4 genome

AF:

0.00210

AC:

320

AN:

152236

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0424

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00192

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00387

AC:

470

Asia WGS

AF:

0.0240

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 provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 09, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.030

T;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0064

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.2

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.95

N;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.032

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.73

MVP

0.46

MPC

0.71

ClinPred

0.028

GERP RS

4.9

Varity_R

0.12

gMVP

0.48

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