Genetic Variant NM_001042462.2:c.296G>T (chr19-7682549-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001042462.2(TRAPPC5):c.296G>T(p.Gly99Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,612,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G99S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TRAPPC5
NM_001042462.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042462.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC5	NM_001042462.2	MANE Select	c.296G>T	p.Gly99Val	missense	Exon 2 of 2	NP_001035927.1	Q8IUR0
TRAPPC5	NM_001042461.3		c.296G>T	p.Gly99Val	missense	Exon 2 of 2	NP_001035926.1	Q8IUR0
TRAPPC5	NM_174894.3		c.296G>T	p.Gly99Val	missense	Exon 2 of 2	NP_777554.1	Q8IUR0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC5	ENST00000596148.3	TSL:1 MANE Select	c.296G>T	p.Gly99Val	missense	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
TRAPPC5	ENST00000317378.5	TSL:1	c.296G>T	p.Gly99Val	missense	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
ENSG00000269711	ENST00000597959.1	TSL:4	c.*60G>T		3_prime_UTR	Exon 3 of 3	ENSP00000469811.1	M0QYG6

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000406

AC:

AN:

246192

AF XY:

0.0000298

show subpopulations

Gnomad AFR exome

AF:

0.000521

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1460426

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726630

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33476

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111946

Other (OTH)

AF:

0.0000828

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000400

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41590

American (AMR)

AF:

0.0000653

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.000155

Hom.:

Bravo

AF:

0.000393

ESP6500AA

AF:

0.000686

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

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

Pathogenic

0.91

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.74

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.5

PhyloP100

7.5

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-8.8

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.78

MVP

0.32

MPC

2.6

ClinPred

0.99

GERP RS

4.1

PromoterAI

0.023

Neutral

(source)

Varity_R

0.98

gMVP

0.96

Mutation Taster

=15/85

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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