Variant 8-140284041-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001160372.4(TRAPPC9):c.1982-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,613,698 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 38 hom. )

Consequence

TRAPPC9
NM_001160372.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.414

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 (BayesDel_noAF=-0.88).

BP6

Variant 8-140284041-T-G is Benign according to our data. Variant chr8-140284041-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 445432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2076/152228) while in subpopulation AFR AF= 0.0471 (1955/41538). AF 95% confidence interval is 0.0453. There are 50 homozygotes in gnomad4. There are 1005 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4 linkuse as main transcript	c.1982-20A>C		intron_variant		ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4 linkuse as main transcript	c.1982-20A>C		intron_variant		1	NM_001160372.4	P1	Q96Q05-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2054

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0467

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00362

AC:

910

AN:

251120

Hom.:

AF XY:

0.00256

AC XY:

347

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.0478

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00155

AC:

2263

AN:

1461470

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

981

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.0136

AC:

2076

AN:

152228

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1005

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0471

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00753

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.28

DANN

Benign

0.35

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