dbSNP rs6952: TRAPPC5:p.Ser52Ala (chr19-7682407-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

26 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2 link	c.154T>G	p.Ser52Ala	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1	Q8IUR0
TRAPPC5	NM_001042461.3 link	c.154T>G	p.Ser52Ala	missense_variant	Exon 2 of 2		NP_001035926.1	Q8IUR0
TRAPPC5	NM_174894.3 link	c.154T>G	p.Ser52Ala	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.154T>G	p.Ser52Ala	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1		Q8IUR0
ENSG00000269711	ENST00000597959.1 link	c.329T>G	p.Val110Gly	missense_variant	Exon 3 of 3	4		ENSP00000469811.1		M0QYG6

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

GnomAD2 exomes

AF:

0.289

AC:

54971

AN:

190532

AF XY:

0.293

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 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

African (AFR)

AF:

0.544

AC:

17560

AN:

32292

American (AMR)

AF:

0.158

AC:

6294

AN:

39740

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

8916

AN:

25168

East Asian (EAS)

AF:

0.235

AC:

8970

AN:

38146

South Asian (SAS)

AF:

0.325

AC:

26927

AN:

82824

European-Finnish (FIN)

AF:

0.312

AC:

15570

AN:

49932

Middle Eastern (MID)

AF:

0.402

AC:

2154

AN:

5360

European-Non Finnish (NFE)

AF:

0.305

AC:

334785

AN:

1096382

Other (OTH)

AF:

0.324

AC:

19093

AN:

58952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

20719

41438

62156

82875

103594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11090

22180

33270

44360

55450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.367

AC:

55883

AN:

152086

Hom.:

11252

Cov.:

AF XY:

0.363

AC XY:

27021

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.540

AC:

22404

AN:

41506

American (AMR)

AF:

0.245

AC:

3741

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1213

AN:

3470

East Asian (EAS)

AF:

0.267

AC:

1377

AN:

5164

South Asian (SAS)

AF:

0.321

AC:

1549

AN:

4828

European-Finnish (FIN)

AF:

0.315

AC:

3337

AN:

10592

Middle Eastern (MID)

AF:

0.434

AC:

126

AN:

290

European-Non Finnish (NFE)

AF:

0.311

AC:

21106

AN:

67934

Other (OTH)

AF:

0.348

AC:

736

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1808

3616

5423

7231

9039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.323

Hom.:

4374

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

Dec 03, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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

PhyloP100

1.1

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

PromoterAI

-0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over