Genetic Variant TRAPPC8:p.Ala1409Ser (chr18-31830838-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_014939.5(TRAPPC8):c.4225G>T(p.Ala1409Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000283 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

TRAPPC8
NM_014939.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Publications

2 publications found

Variant links:

Genes affected

TRAPPC8 (HGNC:29169): (trafficking protein particle complex subunit 8) Involved in Golgi organization. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31222367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014939.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC8	NM_014939.5	MANE Select	c.4225G>T	p.Ala1409Ser	missense	Exon 29 of 29	NP_055754.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC8	ENST00000283351.10	TSL:1 MANE Select	c.4225G>T	p.Ala1409Ser	missense	Exon 29 of 29	ENSP00000283351.4	Q9Y2L5-1
TRAPPC8	ENST00000582539.5	TSL:1	c.4063G>T	p.Ala1355Ser	missense	Exon 29 of 29	ENSP00000463764.1	J3QQJ5
TRAPPC8	ENST00000865828.1		c.4228G>T	p.Ala1410Ser	missense	Exon 29 of 29	ENSP00000535887.1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000215

AC:

AN:

251434

AF XY:

0.000235

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000287

AC:

419

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

203

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000359

AC:

399

AN:

1112004

Other (OTH)

AF:

0.000199

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000250

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000406

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0035

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.042

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

PhyloP100

7.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

REVEL

Benign

0.26

Sift

Uncertain

0.011

Sift4G

Uncertain

0.051

Polyphen

0.96

Vest4

0.67

MVP

0.043

MPC

0.55

ClinPred

0.21

GERP RS

5.8

Varity_R

0.27

gMVP

0.41

Mutation Taster

=76/24

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over