Variant 6-116496989-T-C 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.511A>G(p.Lys171Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

TRAPPC3L
NM_001139444.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

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 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=0.15526745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC3L	NM_001139444.3 linkuse as main transcript	c.511A>G	p.Lys171Glu	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.511A>G	p.Lys171Glu	missense_variant	5/5	5	NM_001139444.3	ENSP00000357591.3	Q5T215-1
TRAPPC3L	ENST00000437098.5 linkuse as main transcript	c.469A>G	p.Lys157Glu	missense_variant	4/4	3		ENSP00000395769.1	A0A0A0MSL6
TRAPPC3L	ENST00000356128.4 linkuse as main transcript	c.259A>G	p.Lys87Glu	missense_variant	3/3	2		ENSP00000348445.4	Q5T215-2
ENSG00000234117	ENST00000420595.2 linkuse as main transcript	n.627T>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1394392

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687602

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:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 18, 2023

The c.511A>G (p.K171E) alteration is located in exon 5 (coding exon 5) of the TRAPPC3L gene. This alteration results from a A to G substitution at nucleotide position 511, causing the lysine (K) at amino acid position 171 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.072

.;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.030

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;.;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.10

.;.;B

Vest4

0.35

MutPred

0.38

.;.;Loss of MoRF binding (P = 0.0029);

MVP

0.055

ClinPred

0.83

GERP RS

4.5

Varity_R

0.36

gMVP

0.41

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