8-139732009-G-A

Position:

chr8-139732009-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001160372.4(TRAPPC9):c.3249C>T(p.Phe1083Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 1,596,098 control chromosomes in the GnomAD database, including 64 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 0.0050 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 61 hom. )

Consequence

TRAPPC9
NM_001160372.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 1.51

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 links:

TRAPPC9 (HGNC:):

TRAPPC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 8-139732009-G-A is Benign according to our data. Variant chr8-139732009-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 130632.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1, Benign=2}.

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.005 (762/152352) while in subpopulation NFE AF= 0.00747 (508/68032). AF 95% confidence interval is 0.00693. There are 3 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4 linkuse as main transcript	c.3249C>T	p.Phe1083Phe	synonymous_variant	22/23	ENST00000438773.4	NP_001153844.1	Q96Q05-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4 linkuse as main transcript	c.3249C>T	p.Phe1083Phe	synonymous_variant	22/23	1	NM_001160372.4	ENSP00000405060.3		Q96Q05-1

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

762

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00747

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00617

AC:

1351

AN:

218814

Hom.:

AF XY:

0.00642

AC XY:

757

AN XY:

117972

show subpopulations

Gnomad AFR exome

AF:

0.00159

Gnomad AMR exome

AF:

0.00469

Gnomad ASJ exome

AF:

0.00480

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00586

Gnomad FIN exome

AF:

0.00818

Gnomad NFE exome

AF:

0.00814

Gnomad OTH exome

AF:

0.00691

GnomAD4 exome

AF:

0.00810

AC:

11701

AN:

1443746

Hom.:

Cov.:

AF XY:

0.00801

AC XY:

5738

AN XY:

716254

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.00471

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00610

Gnomad4 FIN exome

AF:

0.00899

Gnomad4 NFE exome

AF:

0.00895

Gnomad4 OTH exome

AF:

0.00794

GnomAD4 genome

AF:

0.00500

AC:

762

AN:

152352

Hom.:

Cov.:

AF XY:

0.00460

AC XY:

343

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.00747

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00544

Hom.:

Bravo

AF:

0.00492

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	TRAPPC9: BP4, BP7, BS2 -

Intellectual Disability, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 17, 2014

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2016

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. -

TRAPPC9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.2

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over