rs148523016

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_031466.8(TRAPPC9):c.-135A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,590,156 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

TRAPPC9
NM_031466.8 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0150

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031356514).

BP6

Variant 8-140458405-T-C is Benign according to our data. Variant chr8-140458405-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 130613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000544 (81/148840) while in subpopulation EAS AF= 0.0146 (75/5152). AF 95% confidence interval is 0.0119. There are 0 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
TRAPPC9	XM_011517326.3 link	c.160A>G	p.Ser54Gly	missense_variant	Exon 1 of 22	XP_011515628.1
TRAPPC9	XM_011517328.3 link	c.160A>G	p.Ser54Gly	missense_variant	Exon 1 of 22	XP_011515630.1
TRAPPC9	XM_047422294.1 link	c.160A>G	p.Ser54Gly	missense_variant	Exon 1 of 21	XP_047278250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000648948.2 link	c.-135A>G		5_prime_UTR_variant	Exon 1 of 23			ENSP00000498020.1		Q96Q05-1

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

148746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0145

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000489

GnomAD3 exomes

AF:

0.00161

AC:

341

AN:

212190

Hom.:

AF XY:

0.00167

AC XY:

192

AN XY:

115232

show subpopulations

Gnomad AFR exome

AF:

0.000580

Gnomad AMR exome

AF:

0.0000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0184

Gnomad SAS exome

AF:

0.00100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.000412

AC:

594

AN:

1441316

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

306

AN XY:

715366

show subpopulations

Gnomad4 AFR exome

AF:

0.000161

Gnomad4 AMR exome

AF:

0.0000239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0111

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000725

Gnomad4 OTH exome

AF:

0.000757

GnomAD4 genome

AF:

0.000544

AC:

AN:

148840

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

AN XY:

72844

show subpopulations

Gnomad4 AFR

AF:

0.0000261

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0146

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.000907

ExAC

AF:

0.00156

AC:

188

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jun 12, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 28, 2017

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, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.2

DANN

Benign

0.41

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.080

REVEL

Benign

0.0030

Sift

Benign

1.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.080

MVP

0.067

MPC

0.46

ClinPred

0.0013

GERP RS

-0.12

gMVP

0.10

Splicing

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