Genetic Variant TRAPPC12:p.Glu49Gln (chr2-3387768-G-C) – 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_016030.6(TRAPPC12):c.145G>C(p.Glu49Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRAPPC12
NM_016030.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.27

Variant links:

Genes affected

TRAPPC12 (HGNC:24284): (trafficking protein particle complex subunit 12) Involved in several processes, including endoplasmic reticulum to Golgi vesicle-mediated transport; positive regulation of protein localization to kinetochore; and regulation of kinetochore assembly. Located in Golgi apparatus; kinetochore; and nucleoplasm. Part of TRAPP complex. Colocalizes with endoplasmic reticulum-Golgi intermediate compartment and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC12 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=0.21714187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC12	NM_016030.6 link	c.145G>C	p.Glu49Gln	missense_variant	Exon 2 of 12	ENST00000324266.10	NP_057114.5	Q8WVT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAPPC12	ENST00000324266.10 link	c.145G>C	p.Glu49Gln	missense_variant	Exon 2 of 12	1	NM_016030.6	ENSP00000324318.5	Q8WVT3
TRAPPC12	ENST00000382110.6 link	c.145G>C	p.Glu49Gln	missense_variant	Exon 2 of 12	2		ENSP00000371544.2	Q8WVT3
TRAPPC12	ENST00000482645.1 link	n.306G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152238

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460576

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726508

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.094

Sift

Benign

0.096

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.87

P;P

Vest4

0.16

MutPred

0.19

Loss of glycosylation at S45 (P = 0.1871);Loss of glycosylation at S45 (P = 0.1871);

MVP

0.59

MPC

0.49

ClinPred

0.85

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over