chr2-3387687-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016030.6(TRAPPC12):c.64G>A(p.Ala22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,565,924 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 15 hom. )

Consequence

TRAPPC12
NM_016030.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.626

Publications

3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

TRAPPC12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035474598).

BP6

Variant 2-3387687-G-A is Benign according to our data. Variant chr2-3387687-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1614588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00224 (341/152292) while in subpopulation AMR AF = 0.00379 (58/15308). AF 95% confidence interval is 0.00301. There are 2 homozygotes in GnomAd4. There are 182 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC12	NM_016030.6	MANE Select	c.64G>A	p.Ala22Thr	missense	Exon 2 of 12	NP_057114.5
	TRAPPC12	NM_001321102.2		c.64G>A	p.Ala22Thr	missense	Exon 2 of 12	NP_001308031.1	Q8WVT3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC12	ENST00000324266.10	TSL:1 MANE Select	c.64G>A	p.Ala22Thr	missense	Exon 2 of 12	ENSP00000324318.5	Q8WVT3
TRAPPC12	ENST00000858088.1		c.64G>A	p.Ala22Thr	missense	Exon 2 of 13	ENSP00000528147.1
TRAPPC12	ENST00000964175.1		c.64G>A	p.Ala22Thr	missense	Exon 2 of 13	ENSP00000634234.1

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

341

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00280

AC:

492

AN:

175864

AF XY:

0.00298

show subpopulations

Gnomad AFR exome

AF:

0.000412

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.000805

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00633

Gnomad NFE exome

AF:

0.00249

Gnomad OTH exome

AF:

0.00313

GnomAD4 exome

AF:

0.00252

AC:

3556

AN:

1413632

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

1802

AN XY:

699028

show subpopulations

African (AFR)

AF:

0.000876

AC:

AN:

31976

American (AMR)

AF:

0.00247

AC:

AN:

37608

Ashkenazi Jewish (ASJ)

AF:

0.000435

AC:

AN:

25292

East Asian (EAS)

AF:

0.0000276

AC:

AN:

36256

South Asian (SAS)

AF:

0.00471

AC:

379

AN:

80500

European-Finnish (FIN)

AF:

0.00563

AC:

281

AN:

49878

Middle Eastern (MID)

AF:

0.00525

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00236

AC:

2563

AN:

1087786

Other (OTH)

AF:

0.00290

AC:

170

AN:

58622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

207

413

620

826

1033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.00224

AC:

341

AN:

152292

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41560

American (AMR)

AF:

0.00379

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00373

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00631

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00262

AC:

178

AN:

68016

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00228

Hom.:

Bravo

AF:

0.00186

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000458

AC:

ESP6500EA

AF:

0.00292

AC:

ExAC

AF:

0.00205

AC:

244

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Inborn genetic diseases (1)

TRAPPC12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.1

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.77

PhyloP100

0.63

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.20

REVEL

Benign

0.071

Sift

Benign

0.40

Sift4G

Benign

0.44

Polyphen

0.43

Vest4

0.032

MVP

0.46

MPC

0.24

ClinPred

0.0015

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.067

Mutation Taster

=99/1

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over