Genetic Variant TRAPPC5:p.Ala18Val (chr19-7682306-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001042462.2(TRAPPC5):c.53C>T(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,485,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TRAPPC5
NM_001042462.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0780

Variant links:

Genes affected

TRAPPC5 (HGNC:23067): (trafficking protein particle complex subunit 5) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC5 links:

ENSG00000269711 (HGNC:):

ENSG00000269711 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=0.010866791).

BP6

Variant 19-7682306-C-T is Benign according to our data. Variant chr19-7682306-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3182007.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2 link	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1	Q8IUR0
TRAPPC5	NM_001042461.3 link	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 2		NP_001035926.1	Q8IUR0
TRAPPC5	NM_174894.3 link	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 2		NP_777554.1	Q8IUR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC5	ENST00000596148.3 link	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1		Q8IUR0
ENSG00000269711	ENST00000597959.1 link	c.228C>T	p.Gly76Gly	synonymous_variant	Exon 3 of 3	4		ENSP00000469811.1		M0QYG6

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1333280

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

656012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000917

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:

0.0000359

Gnomad4 OTH exome

AF:

0.0000182

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

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

Bravo

AF:

0.00000756

ExAC

AF:

0.0000374

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 20, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.77

.;.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.2

.;N;N;.

REVEL

Benign

0.038

Sift

Benign

0.057

.;T;T;.

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.0020

B;B;B;.

Vest4

0.012

MutPred

0.27

Loss of disorder (P = 0.0512);Loss of disorder (P = 0.0512);Loss of disorder (P = 0.0512);Loss of disorder (P = 0.0512);

MVP

0.043

MPC

1.2

ClinPred

0.086

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.59

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