Variant 6-116500539-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001139444.3(TRAPPC3L):c.368G>A(p.Arg123Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000838 in 1,551,534 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 1 hom. )

Consequence

TRAPPC3L
NM_001139444.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

Variant links:

Genes affected

TRAPPC3L (HGNC:21090): (trafficking protein particle complex subunit 3L) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and intra-Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.092754066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC3L	NM_001139444.3 linkuse as main transcript	c.368G>A	p.Arg123Gln	missense_variant	4/5	ENST00000368602.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC3L	ENST00000368602.4 linkuse as main transcript	c.368G>A	p.Arg123Gln	missense_variant	4/5	5	NM_001139444.3	P1	Q5T215-1
TRAPPC3L	ENST00000437098.5 linkuse as main transcript	c.326G>A	p.Arg109Gln	missense_variant	3/4	3
TRAPPC3L	ENST00000356128.4 linkuse as main transcript	c.116G>A	p.Arg39Gln	missense_variant	2/3	2			Q5T215-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000141

AC:

AN:

155870

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

82610

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.000405

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:

0.000100

Gnomad OTH exome

AF:

0.000685

GnomAD4 exome

AF:

0.0000815

AC:

114

AN:

1399358

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

690184

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000532

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000667

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.000105

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.0000710

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.368G>A (p.R123Q) alteration is located in exon 4 (coding exon 4) of the TRAPPC3L gene. This alteration results from a G to A substitution at nucleotide position 368, causing the arginine (R) at amino acid position 123 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Pathogenic

1.0

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.093

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

1.0

.;.;D

Vest4

0.35

MVP

0.10

ClinPred

0.061

GERP RS

5.4

Varity_R

0.25

gMVP

0.33

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