rs141067069

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001160372.4(TRAPPC9):c.3241G>A(p.Val1081Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,599,024 control chromosomes in the GnomAD database, including 1 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

TRAPPC9
NM_001160372.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.619

Publications

6 publications found

Variant links:

Genes affected

TRAPPC9 (HGNC:30832): (trafficking protein particle complex subunit 9) This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

TRAPPC9 Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 13
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
intellectual disability-obesity-brain malformations-facial dysmorphism syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRAPPC9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009168237).

BP6

Variant 8-139732017-C-T is Benign according to our data. Variant chr8-139732017-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 437048.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000702 (107/152354) while in subpopulation AFR AF = 0.00236 (98/41590). AF 95% confidence interval is 0.00198. There are 0 homozygotes in GnomAd4. There are 43 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC9	NM_001160372.4	MANE Select	c.3241G>A	p.Val1081Ile	missense	Exon 22 of 23	NP_001153844.1	Q96Q05-1
TRAPPC9	NM_001374682.1		c.3262G>A	p.Val1088Ile	missense	Exon 23 of 24	NP_001361611.1
TRAPPC9	NM_031466.8		c.3241G>A	p.Val1081Ile	missense	Exon 22 of 23	NP_113654.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC9	ENST00000438773.4	TSL:1 MANE Select	c.3241G>A	p.Val1081Ile	missense	Exon 22 of 23	ENSP00000405060.3	Q96Q05-1
TRAPPC9	ENST00000520857.5	TSL:1	c.2770G>A	p.Val924Ile	missense	Exon 20 of 21	ENSP00000430116.1	H0YBR0
TRAPPC9	ENST00000521667.5	TSL:1	n.1646G>A		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000211

AC:

AN:

223030

AF XY:

0.000166

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.0000933

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.000119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000302

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000995

AC:

144

AN:

1446670

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

718012

show subpopulations

African (AFR)

AF:

0.00217

AC:

AN:

33222

American (AMR)

AF:

0.000140

AC:

AN:

42792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25780

East Asian (EAS)

AF:

0.0000256

AC:

AN:

38994

South Asian (SAS)

AF:

0.0000837

AC:

AN:

83590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000398

AC:

AN:

1104642

Other (OTH)

AF:

0.000234

AC:

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000702

AC:

107

AN:

152354

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

41590

American (AMR)

AF:

0.000392

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.000343

Hom.:

Bravo

AF:

0.000842

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000207

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Inborn genetic diseases (1)

not specified (1)

TRAPPC9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.6

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.019

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.56

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PhyloP100

0.62

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.12

REVEL

Benign

0.010

Sift

Benign

0.19

Sift4G

Benign

0.44

Polyphen

0.024

Vest4

0.20

MVP

0.076

MPC

0.060

ClinPred

0.0044

GERP RS

-4.0

Varity_R

0.030

gMVP

0.44

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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