rs148976893

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001160372.4(TRAPPC9):c.1164C>T(p.Tyr388Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.000821 in 1,613,538 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 3 hom. )

Consequence

TRAPPC9
NM_001160372.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 3.94

Publications

0 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 8-140371151-G-A is Benign according to our data. Variant chr8-140371151-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212414.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00126 (192/152280) while in subpopulation NFE AF = 0.0016 (109/68046). AF 95% confidence interval is 0.00136. There are 1 homozygotes in GnomAd4. There are 105 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4 link	c.1164C>T	p.Tyr388Tyr	synonymous_variant	Exon 8 of 23	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TRAPPC9	ENST00000438773.4 link	c.1164C>T	p.Tyr388Tyr	synonymous_variant	Exon 8 of 23	1	NM_001160372.4	ENSP00000405060.3
TRAPPC9	ENST00000520857.5 link	c.693C>T	p.Tyr231Tyr	synonymous_variant	Exon 6 of 21	1		ENSP00000430116.1
TRAPPC9	ENST00000648948.2 link	c.1164C>T	p.Tyr388Tyr	synonymous_variant	Exon 8 of 23			ENSP00000498020.1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00113

AC:

281

AN:

248294

AF XY:

0.00109

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00618

Gnomad NFE exome

AF:

0.000987

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000775

AC:

1133

AN:

1461258

Hom.:

Cov.:

AF XY:

0.000813

AC XY:

591

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.0000896

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00184

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00539

AC:

287

AN:

53246

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000674

AC:

749

AN:

1111760

Other (OTH)

AF:

0.000663

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

147

221

294

368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00126

AC:

192

AN:

152280

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41482

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5208

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00687

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00160

AC:

109

AN:

68046

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00130

Hom.:

Bravo

AF:

0.000646

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TRAPPC9: BP4 -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual Disability, Recessive

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 30, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 17, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.6

(source)

DANN

Benign

0.55

PhyloP100

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over