8-139730730-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_001160372.4(TRAPPC9):c.*331C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 381,794 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00041 ( 3 hom. )
Consequence
TRAPPC9
NM_001160372.4 3_prime_UTR
NM_001160372.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.574
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000112 (17/152292) while in subpopulation EAS AF= 0.00252 (13/5160). AF 95% confidence interval is 0.00149. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRAPPC9 | NM_001160372.4 | c.*331C>T | 3_prime_UTR_variant | 23/23 | ENST00000438773.4 | NP_001153844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRAPPC9 | ENST00000438773 | c.*331C>T | 3_prime_UTR_variant | 23/23 | 1 | NM_001160372.4 | ENSP00000405060.3 | |||
TRAPPC9 | ENST00000520857 | c.*331C>T | 3_prime_UTR_variant | 21/21 | 1 | ENSP00000430116.1 | ||||
TRAPPC9 | ENST00000648948 | c.*331C>T | 3_prime_UTR_variant | 23/23 | ENSP00000498020.1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152174Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000405 AC: 93AN: 229502Hom.: 3 Cov.: 0 AF XY: 0.000349 AC XY: 42AN XY: 120204
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74452
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
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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BayesDel_noAF
Benign
CADD
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at