dbSNP rs539921515: TRAPPC5:p.Gly99Ser (chr19-7682548-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042462.2(TRAPPC5):c.295G>A(p.Gly99Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,458 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TRAPPC5
NM_001042462.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.35

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2 link	c.295G>A	p.Gly99Ser	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1	Q8IUR0
TRAPPC5	NM_001042461.3 link	c.295G>A	p.Gly99Ser	missense_variant	Exon 2 of 2		NP_001035926.1	Q8IUR0
TRAPPC5	NM_174894.3 link	c.295G>A	p.Gly99Ser	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.295G>A	p.Gly99Ser	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1		Q8IUR0
ENSG00000269711	ENST00000597959.1 link	c.*59G>A		3_prime_UTR_variant	Exon 3 of 3	4		ENSP00000469811.1		M0QYG6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246210

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134146

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460458

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726642

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:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000825

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.295G>A (p.G99S) alteration is located in exon 2 (coding exon 1) of the TRAPPC5 gene. This alteration results from a G to A substitution at nucleotide position 295, causing the glycine (G) at amino acid position 99 to be replaced by a serine (S). 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

0.30

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

1.0

.;.;D;D

M_CAP

Uncertain

0.086

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.5

M;M;M;.

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.8

.;D;D;.

REVEL

Uncertain

0.36

Sift

Benign

0.082

.;T;T;.

Sift4G

Uncertain

0.033

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.55

MutPred

0.72

Gain of disorder (P = 0.1055);Gain of disorder (P = 0.1055);Gain of disorder (P = 0.1055);.;

MVP

0.17

MPC

2.4

ClinPred

0.99

GERP RS

3.0

Varity_R

0.75

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over