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GeneBe

rs148805943

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_001160372.4(TRAPPC9):c.3012C>T(p.Asn1004=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,574,250 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

TRAPPC9
NM_001160372.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.03
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 8-139885922-G-A is Benign according to our data. Variant chr8-139885922-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.03 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00155 (236/152326) while in subpopulation NFE AF= 0.00221 (150/68020). AF 95% confidence interval is 0.00192. There are 0 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRAPPC9NM_001160372.4 linkuse as main transcriptc.3012C>T p.Asn1004= synonymous_variant 21/23 ENST00000438773.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRAPPC9ENST00000438773.4 linkuse as main transcriptc.3012C>T p.Asn1004= synonymous_variant 21/231 NM_001160372.4 P1Q96Q05-1

Frequencies

GnomAD3 genomes
AF:
0.00155
AC:
236
AN:
152208
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000458
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00209
Gnomad ASJ
AF:
0.00432
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00220
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00180
AC:
339
AN:
188720
Hom.:
0
AF XY:
0.00185
AC XY:
186
AN XY:
100784
show subpopulations
Gnomad AFR exome
AF:
0.000435
Gnomad AMR exome
AF:
0.00207
Gnomad ASJ exome
AF:
0.00337
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00156
Gnomad FIN exome
AF:
0.0000600
Gnomad NFE exome
AF:
0.00242
Gnomad OTH exome
AF:
0.00284
GnomAD4 exome
AF:
0.00223
AC:
3171
AN:
1421924
Hom.:
7
Cov.:
32
AF XY:
0.00226
AC XY:
1591
AN XY:
703382
show subpopulations
Gnomad4 AFR exome
AF:
0.000427
Gnomad4 AMR exome
AF:
0.00216
Gnomad4 ASJ exome
AF:
0.00323
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00160
Gnomad4 FIN exome
AF:
0.0000599
Gnomad4 NFE exome
AF:
0.00246
Gnomad4 OTH exome
AF:
0.00287
GnomAD4 genome
AF:
0.00155
AC:
236
AN:
152326
Hom.:
0
Cov.:
33
AF XY:
0.00137
AC XY:
102
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000457
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00432
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00221
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00191
Hom.:
0
Bravo
AF:
0.00159
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022TRAPPC9: BP4 -
Likely benign, criteria provided, single submitterclinical testingGeneDxFeb 20, 2021- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 08, 2018- -
TRAPPC9-related condition Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 06, 2021This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 16, 2016This alteration is classified as likely benign based on a combination of the following: 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
-0.36
Cadd
Benign
8.1
Dann
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs148805943; hg19: chr8-140898166; API