Variant 6-116496965-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001139444.3(TRAPPC3L):c.535G>A(p.Gly179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,543,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 0 hom. )

Consequence

TRAPPC3L
NM_001139444.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.53

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:

ENSG00000234117 (HGNC:):

ENSG00000234117 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011007369).

BP6

Variant 6-116496965-C-T is Benign according to our data. Variant chr6-116496965-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2365792.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC3L	NM_001139444.3 linkuse as main transcript	c.535G>A	p.Gly179Arg	missense_variant	5/5	ENST00000368602.4	NP_001132916.1	Q5T215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRAPPC3L	ENST00000368602.4 linkuse as main transcript	c.535G>A	p.Gly179Arg	missense_variant	5/5	5	NM_001139444.3	ENSP00000357591.3	Q5T215-1
TRAPPC3L	ENST00000437098.5 linkuse as main transcript	c.493G>A	p.Gly165Arg	missense_variant	4/4	3		ENSP00000395769.1	A0A0A0MSL6
TRAPPC3L	ENST00000356128.4 linkuse as main transcript	c.283G>A	p.Gly95Arg	missense_variant	3/3	2		ENSP00000348445.4	Q5T215-2
ENSG00000234117	ENST00000420595.2 linkuse as main transcript	n.603C>T		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000519

AC:

AN:

148256

Hom.:

AF XY:

0.000408

AC XY:

AN XY:

78430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000539

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000599

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000987

AC:

1374

AN:

1391698

Hom.:

Cov.:

AF XY:

0.000933

AC XY:

640

AN XY:

686274

show subpopulations

Gnomad4 AFR exome

AF:

0.0000650

Gnomad4 AMR exome

AF:

0.000720

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.000866

GnomAD4 genome

AF:

0.000618

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000889

Hom.:

Bravo

AF:

0.000756

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.000449

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.22

.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.36

T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Benign

0.073

Sift

Benign

0.92

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.14

MutPred

0.23

.;.;Gain of methylation at K180 (P = 0.0283);

MVP

0.13

ClinPred

0.048

GERP RS

4.8

Varity_R

0.12

gMVP

0.16

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