chr2-3387768-G-A

Position:

chr2-3387768-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016030.6(TRAPPC12):c.145G>A(p.Glu49Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000732 in 1,612,926 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 2 hom. )

Consequence

TRAPPC12
NM_016030.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049600303).

BP6

Variant 2-3387768-G-A is Benign according to our data. Variant chr2-3387768-G-A is described in ClinVar as [Benign]. Clinvar id is 1530005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000893 (136/152356) while in subpopulation EAS AF= 0.0162 (84/5188). AF 95% confidence interval is 0.0134. There are 1 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC12	NM_016030.6 link	c.145G>A	p.Glu49Lys	missense_variant	2/12	ENST00000324266.10	NP_057114.5	Q8WVT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRAPPC12	ENST00000324266.10 link	c.145G>A	p.Glu49Lys	missense_variant	2/12	1	NM_016030.6	ENSP00000324318.5	Q8WVT3
TRAPPC12	ENST00000382110.6 link	c.145G>A	p.Glu49Lys	missense_variant	2/12	2		ENSP00000371544.2	Q8WVT3
TRAPPC12	ENST00000482645.1 link	n.306G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000900

AC:

137

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00185

AC:

459

AN:

248264

Hom.:

AF XY:

0.00155

AC XY:

208

AN XY:

134372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00582

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.0126

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.0000625

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.000715

AC:

1045

AN:

1460570

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

468

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00538

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.000407

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000893

AC:

136

AN:

152356

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0162

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000626

Hom.:

Bravo

AF:

0.00104

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00174

AC:

211

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

TRAPPC12-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.093

Sift

Benign

0.042

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.98

D;D

Vest4

0.22

MVP

0.62

MPC

0.48

ClinPred

0.060

GERP RS

5.0

Varity_R

0.16

gMVP

0.20

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