NM_016030.6:c.145G>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.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

Publications

1 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=0.0049600303).

BP6

Variant 2-3387768-G-A is Benign according to our data. Variant chr2-3387768-G-A is described in ClinVar as Benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 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.145G>A	p.Glu49Lys	missense	Exon 2 of 12	NP_057114.5
	TRAPPC12	NM_001321102.2		c.145G>A	p.Glu49Lys	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.145G>A	p.Glu49Lys	missense	Exon 2 of 12	ENSP00000324318.5	Q8WVT3
TRAPPC12	ENST00000858088.1		c.145G>A	p.Glu49Lys	missense	Exon 2 of 13	ENSP00000528147.1
TRAPPC12	ENST00000964175.1		c.145G>A	p.Glu49Lys	missense	Exon 2 of 13	ENSP00000634234.1

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

GnomAD2 exomes

AF:

0.00185

AC:

459

AN:

248264

AF XY:

0.00155

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 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

African (AFR)

AF:

0.0000299

AC:

AN:

33430

American (AMR)

AF:

0.00538

AC:

240

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26102

East Asian (EAS)

AF:

0.0164

AC:

650

AN:

39600

South Asian (SAS)

AF:

0.000407

AC:

AN:

85996

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1111388

Other (OTH)

AF:

0.00123

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000893

AC:

136

AN:

152356

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41582

American (AMR)

AF:

0.00216

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.0162

AC:

AN:

5188

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000650

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

TRAPPC12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

PhyloP100

7.3

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

REVEL

Benign

0.093

Sift

Benign

0.042

Sift4G

Benign

0.24

Polyphen

0.98

Vest4

0.22

MVP

0.62

MPC

0.48

ClinPred

0.060

GERP RS

5.0

Varity_R

0.16

gMVP

0.20

Mutation Taster

=98/2

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