2-3388304-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016030.6(TRAPPC12):c.681T>C(p.Phe227Phe) 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

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

TRAPPC12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC12	NM_016030.6	MANE Select	c.681T>C	p.Phe227Phe	synonymous	Exon 2 of 12	NP_057114.5
	TRAPPC12	NM_001321102.2		c.681T>C	p.Phe227Phe	synonymous	Exon 2 of 12	NP_001308031.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAPPC12	ENST00000324266.10	TSL:1 MANE Select	c.681T>C	p.Phe227Phe	synonymous	Exon 2 of 12	ENSP00000324318.5
TRAPPC12	ENST00000382110.6	TSL:2	c.681T>C	p.Phe227Phe	synonymous	Exon 2 of 12	ENSP00000371544.2
TRAPPC12	ENST00000411973.3	TSL:5	n.177T>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000405626.1

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

GnomAD2 exomes

AF:

0.596

AC:

140587

AN:

235766

AF XY:

0.601

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 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

African (AFR)

AF:

0.703

AC:

22654

AN:

32224

American (AMR)

AF:

0.470

AC:

20784

AN:

44228

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

16297

AN:

25856

East Asian (EAS)

AF:

0.677

AC:

26402

AN:

38974

South Asian (SAS)

AF:

0.651

AC:

55681

AN:

85476

European-Finnish (FIN)

AF:

0.613

AC:

32358

AN:

52812

Middle Eastern (MID)

AF:

0.667

AC:

3825

AN:

5734

European-Non Finnish (NFE)

AF:

0.581

AC:

644342

AN:

1109088

Other (OTH)

AF:

0.608

AC:

36556

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21088

42176

63264

84352

105440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17882

35764

53646

71528

89410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.621

AC:

94329

AN:

151912

Hom.:

29565

Cov.:

AF XY:

0.621

AC XY:

46145

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.704

AC:

29181

AN:

41468

American (AMR)

AF:

0.529

AC:

8088

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

2178

AN:

3470

East Asian (EAS)

AF:

0.695

AC:

3545

AN:

5098

South Asian (SAS)

AF:

0.652

AC:

3143

AN:

4824

European-Finnish (FIN)

AF:

0.616

AC:

6514

AN:

10578

Middle Eastern (MID)

AF:

0.654

AC:

191

AN:

292

European-Non Finnish (NFE)

AF:

0.582

AC:

39491

AN:

67886

Other (OTH)

AF:

0.612

AC:

1288

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1882

3764

5646

7528

9410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.598

Hom.:

55155

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Dec 07, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TRAPPC12-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.5

(source)

DANN

Benign

0.43

PhyloP100

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over