rs761865592
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016213.5(TRIP4):c.832C>T(p.Arg278Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000806 in 1,613,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
TRIP4
NM_016213.5 stop_gained
NM_016213.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 3.78
Genes affected
TRIP4 (HGNC:12310): (thyroid hormone receptor interactor 4) This gene encodes a subunit of the tetrameric nuclear activating signal cointegrator 1 (ASC-1) complex, which associates with transcriptional coactivators, nuclear receptors and basal transcription factors to facilitate nuclear receptors-mediated transcription. This protein is localized in the nucleus and contains an E1A-type zinc finger domain, which mediates interaction with transcriptional coactivators and ligand-bound nuclear receptors, such as thyroid hormone receptor and retinoid X receptor alpha, but not glucocorticoid receptor. Mutations in this gene are associated with spinal muscular atrophy with congenital bone fractures-1 (SMABF1). [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-64409617-C-T is Pathogenic according to our data. Variant chr15-64409617-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 224632.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-64409617-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIP4 | NM_016213.5 | c.832C>T | p.Arg278Ter | stop_gained | 7/13 | ENST00000261884.8 | |
TRIP4 | NM_001321924.2 | c.142C>T | p.Arg48Ter | stop_gained | 7/13 | ||
TRIP4 | NR_135855.2 | n.860C>T | non_coding_transcript_exon_variant | 7/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIP4 | ENST00000261884.8 | c.832C>T | p.Arg278Ter | stop_gained | 7/13 | 1 | NM_016213.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251346Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135852
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461558Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727082
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Apr 27, 2019 | - - |
Spinal muscular atrophy with congenital bone fractures 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at