Variant chr14-39151782-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001079537.2(TRAPPC6B):c.409A>T(p.Ser137Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,609,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

TRAPPC6B
NM_001079537.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.53

Variant links:

Genes affected

TRAPPC6B (HGNC:23066): (trafficking protein particle complex subunit 6B) TRAPPC6B is a component of TRAPP complexes, which are tethering complexes involved in vesicle transport (Kummel et al., 2005 [PubMed 16025134]).[supplied by OMIM, Mar 2008]

TRAPPC6B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC6B	NM_001079537.2 linkuse as main transcript	c.409A>T	p.Ser137Cys	missense_variant	5/6	ENST00000330149.10
TRAPPC6B	NM_177452.4 linkuse as main transcript	c.325A>T	p.Ser109Cys	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC6B	ENST00000330149.10 linkuse as main transcript	c.409A>T	p.Ser137Cys	missense_variant	5/6	1	NM_001079537.2	P1	Q86SZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000811

AC:

AN:

246728

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133342

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000357

AC:

AN:

1457028

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

724624

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000423

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	TRAPPC6B: PM2 -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 28, 2023	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 137 of the TRAPPC6B protein (p.Ser137Cys). This variant is present in population databases (rs751288725, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TRAPPC6B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1918086). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.067

T;.

Eigen

Benign

0.085

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.83

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.22

Sift

Benign

0.32

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.073

B;B

Vest4

0.88

MutPred

0.75

Gain of catalytic residue at N132 (P = 5e-04);.;

MVP

0.47

MPC

0.42

ClinPred

0.31

GERP RS

6.0

Varity_R

0.59

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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