Variant rs6952 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001042462.2(TRAPPC5):c.154T>G(p.Ser52Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,580,882 control chromosomes in the GnomAD database, including 80,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 11252 hom., cov: 33)

Exomes 𝑓: 0.31 ( 69715 hom. )

Consequence

TRAPPC5
NM_001042462.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.4992228E-4).

BP6

Variant 19-7682407-T-G is Benign according to our data. Variant chr19-7682407-T-G is described in ClinVar as [Benign]. Clinvar id is 1327245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRAPPC5	NM_001042462.2 linkuse as main transcript	c.154T>G	p.Ser52Ala	missense_variant	2/2	ENST00000596148.3	NP_001035927.1
TRAPPC5	NM_001042461.3 linkuse as main transcript	c.154T>G	p.Ser52Ala	missense_variant	2/2		NP_001035926.1
TRAPPC5	NM_174894.3 linkuse as main transcript	c.154T>G	p.Ser52Ala	missense_variant	2/2		NP_777554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRAPPC5	ENST00000596148.3 linkuse as main transcript	c.154T>G	p.Ser52Ala	missense_variant	2/2	1	NM_001042462.2	ENSP00000470262	P1
TRAPPC5	ENST00000317378.5 linkuse as main transcript	c.154T>G	p.Ser52Ala	missense_variant	2/2	1		ENSP00000316990	P1
TRAPPC5	ENST00000426877.2 linkuse as main transcript	c.154T>G	p.Ser52Ala	missense_variant	2/2	2		ENSP00000399025	P1
TRAPPC5	ENST00000595985.1 linkuse as main transcript	c.69+85T>G		intron_variant		3		ENSP00000470703

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55848

AN:

151978

Hom.:

11238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.429

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.289

AC:

54971

AN:

190532

Hom.:

8756

AF XY:

0.293

AC XY:

30778

AN XY:

104932

show subpopulations

Gnomad AFR exome

AF:

0.527

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.257

Gnomad SAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.308

AC:

440269

AN:

1428796

Hom.:

69715

Cov.:

AF XY:

0.309

AC XY:

218790

AN XY:

708360

show subpopulations

Gnomad4 AFR exome

AF:

0.544

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.325

Gnomad4 FIN exome

AF:

0.312

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.324

GnomAD4 genome

AF:

0.367

AC:

55883

AN:

152086

Hom.:

11252

Cov.:

AF XY:

0.363

AC XY:

27021

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.540

Gnomad4 AMR

AF:

0.245

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.315

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.348

Alfa

AF:

0.329

Hom.:

2688

Bravo

AF:

0.367

TwinsUK

AF:

0.321

AC:

1191

ALSPAC

AF:

0.310

AC:

1196

ESP6500AA

AF:

0.454

AC:

1566

ESP6500EA

AF:

0.270

AC:

1982

ExAC

AF:

0.251

AC:

27773

Asia WGS

AF:

0.279

AC:

968

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 03, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0053

T;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.26

.;.;T

MetaRNN

Benign

0.00025

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.28

N;N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.058

Sift

Benign

0.53

.;T;T

Sift4G

Benign

0.75

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.028

MPC

0.99

ClinPred

0.0079

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.56

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