8-139730529-C-T
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001160372.4(TRAPPC9):c.*532G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 159,044 control chromosomes in the GnomAD database, including 6 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 0.0065 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0081 ( 0 hom. )
Consequence
TRAPPC9
NM_001160372.4 3_prime_UTR
NM_001160372.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.54
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 8-139730529-C-T is Benign according to our data. Variant chr8-139730529-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 362052.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00649 (987/152168) while in subpopulation NFE AF= 0.0103 (702/67970). AF 95% confidence interval is 0.00969. There are 6 homozygotes in gnomad4. There are 490 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRAPPC9 | ENST00000438773 | c.*532G>A | 3_prime_UTR_variant | 23/23 | 1 | NM_001160372.4 | ENSP00000405060.3 | |||
TRAPPC9 | ENST00000520857 | c.*532G>A | 3_prime_UTR_variant | 21/21 | 1 | ENSP00000430116.1 | ||||
TRAPPC9 | ENST00000648948 | c.*532G>A | 3_prime_UTR_variant | 23/23 | ENSP00000498020.1 |
Frequencies
GnomAD3 genomes AF: 0.00649 AC: 987AN: 152050Hom.: 6 Cov.: 32
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GnomAD4 exome AF: 0.00814 AC: 56AN: 6876Hom.: 0 Cov.: 0 AF XY: 0.00701 AC XY: 25AN XY: 3564
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GnomAD4 genome AF: 0.00649 AC: 987AN: 152168Hom.: 6 Cov.: 32 AF XY: 0.00659 AC XY: 490AN XY: 74400
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | TRAPPC9: BS1, BS2 - |
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Intellectual Disability, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at