rs4821708
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001039141.3(TRIOBP):c.6498C>T(p.Tyr2166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,611,854 control chromosomes in the GnomAD database, including 77,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5711 hom., cov: 31)
Exomes 𝑓: 0.31 ( 71546 hom. )
Consequence
TRIOBP
NM_001039141.3 synonymous
NM_001039141.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.04
Genes affected
TRIOBP (HGNC:17009): (TRIO and F-actin binding protein) This gene encodes a protein with an N-terminal pleckstrin homology domain and a C-terminal coiled-coil region. The protein interacts with trio, which is involved with neural tissue development and controlling actin cytoskeleton organization, cell motility and cell growth. The protein also associates with F-actin and stabilizes F-actin structures. Mutations in this gene have been associated with a form of autosomal recessive nonsyndromic deafness. Multiple alternatively spliced transcript variants that would encode different isoforms have been found for this gene, however some transcripts may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 22-37768099-C-T is Benign according to our data. Variant chr22-37768099-C-T is described in ClinVar as [Benign]. Clinvar id is 43866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37768099-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.6498C>T | p.Tyr2166= | synonymous_variant | 19/24 | ENST00000644935.1 | |
TRIOBP | NM_007032.5 | c.1359C>T | p.Tyr453= | synonymous_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.6498C>T | p.Tyr2166= | synonymous_variant | 19/24 | NM_001039141.3 | A2 | ||
TRIOBP | ENST00000403663.6 | c.1359C>T | p.Tyr453= | synonymous_variant | 9/14 | 1 | P2 | ||
TRIOBP | ENST00000344404.10 | c.*5981C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/22 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.251 AC: 38122AN: 151928Hom.: 5718 Cov.: 31
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GnomAD3 exomes AF: 0.315 AC: 77487AN: 246366Hom.: 12775 AF XY: 0.323 AC XY: 43132AN XY: 133580
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GnomAD4 exome AF: 0.308 AC: 449136AN: 1459808Hom.: 71546 Cov.: 39 AF XY: 0.312 AC XY: 226162AN XY: 725986
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GnomAD4 genome ? AF: 0.251 AC: 38123AN: 152046Hom.: 5711 Cov.: 31 AF XY: 0.257 AC XY: 19069AN XY: 74334
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Tyr2166Tyr in Exon 19 of TRIOBP: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 30.4% (2057/6762) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs4821708). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at