Genetic Variant TRAPPC5:p.Ala16Gly (chr19-7682300-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042462.2(TRAPPC5):c.47C>G(p.Ala16Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000378 in 1,323,092 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: not found (cov: 32)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

TRAPPC5
NM_001042462.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.122564465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2 link	c.47C>G	p.Ala16Gly	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1	Q8IUR0
TRAPPC5	NM_001042461.3 link	c.47C>G	p.Ala16Gly	missense_variant	Exon 2 of 2		NP_001035926.1	Q8IUR0
TRAPPC5	NM_174894.3 link	c.47C>G	p.Ala16Gly	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.47C>G	p.Ala16Gly	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1		Q8IUR0
ENSG00000269711	ENST00000597959.1 link	c.222C>G	p.Arg74Arg	synonymous_variant	Exon 3 of 3	4		ENSP00000469811.1		M0QYG6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000378

AC:

AN:

1323092

Hom.:

Cov.:

AF XY:

0.00000308

AC XY:

AN XY:

650340

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000475

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47C>G (p.A16G) alteration is located in exon 2 (coding exon 1) of the TRAPPC5 gene. This alteration results from a C to G substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

T;T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.011

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

.;.;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.0

.;N;N;.

REVEL

Benign

0.039

Sift

Benign

0.032

.;D;D;.

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.083

B;B;B;.

Vest4

0.059

MutPred

0.30

Loss of stability (P = 0.0393);Loss of stability (P = 0.0393);Loss of stability (P = 0.0393);Loss of stability (P = 0.0393);

MVP

0.068

MPC

1.2

ClinPred

0.54

GERP RS

3.5

Varity_R

0.25

gMVP

0.76

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over