rs3735801

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001160372.4(TRAPPC9):c.207T>C(p.Gly69Gly) 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 1,613,186 control chromosomes in the GnomAD database, including 254,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 23735 hom., cov: 29)

Exomes 𝑓: 0.56 ( 230517 hom. )

Consequence

TRAPPC9
NM_001160372.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.97

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 8-140451167-A-G is Benign according to our data. Variant chr8-140451167-A-G is described in ClinVar as [Benign]. Clinvar id is 130634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-140451167-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4 link	c.207T>C	p.Gly69Gly	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.207T>C	p.Gly69Gly	synonymous_variant	Exon 2 of 23	1	NM_001160372.4	ENSP00000405060.3	Q96Q05-1
TRAPPC9	ENST00000648948.2 link	c.207T>C	p.Gly69Gly	synonymous_variant	Exon 2 of 23			ENSP00000498020.1	Q96Q05-1
TRAPPC9	ENST00000520857.5 link	c.-238T>C		upstream_gene_variant		1		ENSP00000430116.1	H0YBR0

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84470

AN:

151236

Hom.:

23713

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.605

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.597

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.556

GnomAD3 exomes

AF:

0.539

AC:

135478

AN:

251340

Hom.:

37324

AF XY:

0.544

AC XY:

73907

AN XY:

135860

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 SAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.595

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.560

AC:

818668

AN:

1461832

Hom.:

230517

Cov.:

AF XY:

0.560

AC XY:

407521

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.540

Gnomad4 AMR exome

AF:

0.389

Gnomad4 ASJ exome

AF:

0.610

Gnomad4 EAS exome

AF:

0.532

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.598

Gnomad4 NFE exome

AF:

0.567

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.558

AC:

84530

AN:

151354

Hom.:

23735

Cov.:

AF XY:

0.557

AC XY:

41157

AN XY:

73908

show subpopulations

Gnomad4 AFR

AF:

0.551

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.605

Gnomad4 EAS

AF:

0.531

Gnomad4 SAS

AF:

0.558

Gnomad4 FIN

AF:

0.597

Gnomad4 NFE

AF:

0.573

Gnomad4 OTH

AF:

0.559

Alfa

AF:

0.566

Hom.:

53951

Bravo

AF:

0.545

Asia WGS

AF:

0.537

AC:

1863

AN:

3478

EpiCase

AF:

0.566

EpiControl

AF:

0.566

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

0.35

DANN

Benign

0.60

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

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