NM_001160372.4:c.288T>C

Variant names:

Variant summary

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

The NM_001160372.4(TRAPPC9):c.288T>C(p.Phe96Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,613,678 control chromosomes in the GnomAD database, including 254,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 23775 hom., cov: 31)

Exomes 𝑓: 0.56 ( 230820 hom. )

Consequence

TRAPPC9
NM_001160372.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.774

Publications

18 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
intellectual disability-obesity-brain malformations-facial dysmorphism syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-140451086-A-G is Benign according to our data. Variant chr8-140451086-A-G is described in ClinVar as [Benign]. Clinvar id is 130635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.774 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4 link	c.288T>C	p.Phe96Phe	synonymous_variant	Exon 2 of 23	ENST00000438773.4	NP_001153844.1	Q96Q05-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAPPC9	ENST00000438773.4 link	c.288T>C	p.Phe96Phe	synonymous_variant	Exon 2 of 23	1	NM_001160372.4	ENSP00000405060.3	Q96Q05-1
TRAPPC9	ENST00000648948.2 link	c.288T>C	p.Phe96Phe	synonymous_variant	Exon 2 of 23			ENSP00000498020.1	Q96Q05-1
TRAPPC9	ENST00000520857.5 link	c.-157T>C		upstream_gene_variant		1		ENSP00000430116.1	H0YBR0

Frequencies

GnomAD3 genomes

AF:

0.558

AC:

84602

AN:

151742

Hom.:

23753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.605

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.597

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.555

GnomAD2 exomes

AF:

0.540

AC:

135646

AN:

251372

AF XY:

0.545

show subpopulations

Gnomad AFR exome

AF:

0.548

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.609

Gnomad EAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.595

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.560

AC:

819183

AN:

1461818

Hom.:

230820

Cov.:

AF XY:

0.561

AC XY:

407877

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.540

AC:

18068

AN:

33480

American (AMR)

AF:

0.389

AC:

17398

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

15942

AN:

26136

East Asian (EAS)

AF:

0.532

AC:

21108

AN:

39700

South Asian (SAS)

AF:

0.556

AC:

47972

AN:

86256

European-Finnish (FIN)

AF:

0.598

AC:

31925

AN:

53366

Middle Eastern (MID)

AF:

0.542

AC:

3124

AN:

5768

European-Non Finnish (NFE)

AF:

0.567

AC:

629976

AN:

1111996

Other (OTH)

AF:

0.557

AC:

33670

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

26207

52413

78620

104826

131033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17508

35016

52524

70032

87540

<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:

0.557

AC:

84662

AN:

151860

Hom.:

23775

Cov.:

AF XY:

0.556

AC XY:

41261

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.549

AC:

22739

AN:

41412

American (AMR)

AF:

0.489

AC:

7464

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.605

AC:

2095

AN:

3464

East Asian (EAS)

AF:

0.532

AC:

2736

AN:

5142

South Asian (SAS)

AF:

0.561

AC:

2700

AN:

4814

European-Finnish (FIN)

AF:

0.597

AC:

6279

AN:

10526

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.572

AC:

38863

AN:

67934

Other (OTH)

AF:

0.558

AC:

1175

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1893

3785

5678

7570

9463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.567

Hom.:

41986

Bravo

AF:

0.545

Asia WGS

AF:

0.542

AC:

1880

AN:

3478

EpiCase

AF:

0.566

EpiControl

AF:

0.565

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inborn genetic diseases

Benign:1

Mar 11, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Intellectual disability, autosomal recessive 13

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual Disability, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.53

(source)

DANN

Benign

0.56

PhyloP100

-0.77

PromoterAI

0.0064

Neutral

(source)

Mutation Taster

=100/0

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over