Genetic Variant NM_001042462.2:c.53C>G (chr19-7682306-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001042462.2(TRAPPC5):c.53C>G(p.Ala18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A18V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRAPPC5
NM_001042462.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06674647).

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.53C>G	p.Ala18Gly	missense	Exon 2 of 2	NP_001035927.1	Q8IUR0
TRAPPC5	NM_001042461.3		c.53C>G	p.Ala18Gly	missense	Exon 2 of 2	NP_001035926.1	Q8IUR0
TRAPPC5	NM_174894.3		c.53C>G	p.Ala18Gly	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.53C>G	p.Ala18Gly	missense	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
TRAPPC5	ENST00000317378.5	TSL:1	c.53C>G	p.Ala18Gly	missense	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
ENSG00000269711	ENST00000597959.1	TSL:4	c.228C>G	p.Gly76Gly	synonymous	Exon 3 of 3	ENSP00000469811.1	M0QYG6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1333280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656012

African (AFR)

AF:

0.00

AC:

AN:

25970

American (AMR)

AF:

0.00

AC:

AN:

21814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21054

East Asian (EAS)

AF:

0.00

AC:

AN:

32720

South Asian (SAS)

AF:

0.00

AC:

AN:

69124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4474

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057960

Other (OTH)

AF:

0.00

AC:

AN:

54948

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.76

M_CAP

Benign

0.012

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.065

PhyloP100

-0.078

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.74

REVEL

Benign

0.023

Sift

Benign

0.16

Sift4G

Benign

0.35

Polyphen

0.0010

Vest4

0.043

MutPred

0.20

Loss of helix (P = 0.0558)

MVP

0.043

MPC

1.2

ClinPred

0.16

GERP RS

-1.5

PromoterAI

-0.042

Neutral

(source)

Varity_R

0.063

gMVP

0.56

Mutation Taster

=85/15

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over