Variant 2-3388304-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016030.6(TRAPPC12):c.681T>C(p.Phe227=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,606,390 control chromosomes in the GnomAD database, including 284,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29565 hom., cov: 32)

Exomes 𝑓: 0.59 ( 254773 hom. )

Consequence

TRAPPC12
NM_016030.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.72

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 2-3388304-T-C is Benign according to our data. Variant chr2-3388304-T-C is described in ClinVar as [Benign]. Clinvar id is 1282559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC12	NM_016030.6 linkuse as main transcript	c.681T>C	p.Phe227=	synonymous_variant	2/12	ENST00000324266.10	NP_057114.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRAPPC12	ENST00000324266.10 linkuse as main transcript	c.681T>C	p.Phe227=	synonymous_variant	2/12	1	NM_016030.6	ENSP00000324318	P1
TRAPPC12	ENST00000382110.6 linkuse as main transcript	c.681T>C	p.Phe227=	synonymous_variant	2/12	2		ENSP00000371544	P1
TRAPPC12	ENST00000482645.1 linkuse as main transcript	n.842T>C		non_coding_transcript_exon_variant	2/2	2
TRAPPC12	ENST00000411973.3 linkuse as main transcript	c.180T>C	p.Phe60=	synonymous_variant, NMD_transcript_variant	1/4	5		ENSP00000405626

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94259

AN:

151804

Hom.:

29529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.703

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.651

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.617

GnomAD3 exomes

AF:

0.596

AC:

140587

AN:

235766

Hom.:

42539

AF XY:

0.601

AC XY:

77199

AN XY:

128406

show subpopulations

Gnomad AFR exome

AF:

0.700

Gnomad AMR exome

AF:

0.461

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.714

Gnomad SAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.615

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.591

AC:

858899

AN:

1454478

Hom.:

254773

Cov.:

AF XY:

0.592

AC XY:

428628

AN XY:

723560

show subpopulations

Gnomad4 AFR exome

AF:

0.703

Gnomad4 AMR exome

AF:

0.470

Gnomad4 ASJ exome

AF:

0.630

Gnomad4 EAS exome

AF:

0.677

Gnomad4 SAS exome

AF:

0.651

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.581

Gnomad4 OTH exome

AF:

0.608

GnomAD4 genome

AF:

0.621

AC:

94329

AN:

151912

Hom.:

29565

Cov.:

AF XY:

0.621

AC XY:

46145

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.704

Gnomad4 AMR

AF:

0.529

Gnomad4 ASJ

AF:

0.628

Gnomad4 EAS

AF:

0.695

Gnomad4 SAS

AF:

0.652

Gnomad4 FIN

AF:

0.616

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.612

Alfa

AF:

0.591

Hom.:

34975

Bravo

AF:

0.617

Asia WGS

AF:

0.679

AC:

2345

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 07, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

TRAPPC12-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.5

DANN

Benign

0.43

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