rs876658036
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001039141.3(TRIOBP):c.3948G>A(p.Arg1316=) variant causes a splice region, synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
TRIOBP
NM_001039141.3 splice_region, synonymous
NM_001039141.3 splice_region, synonymous
Scores
2
Splicing: ADA: 0.9986
2
Clinical Significance
Conservation
PhyloP100: 6.14
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.3948G>A | p.Arg1316= | splice_region_variant, synonymous_variant | 8/24 | ENST00000644935.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.3948G>A | p.Arg1316= | splice_region_variant, synonymous_variant | 8/24 | NM_001039141.3 | A2 | ||
TRIOBP | ENST00000344404.10 | c.*3431G>A | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 6/22 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 04, 2015 | The p.Arg1316Arg variant in TRIOBP has not been previously reported in individua ls with hearing loss. Data from large population studies are insufficient to ass ess the frequency of this variant. This variant is located in the first base of the exon, which is part of the 3? splice region. Computational tools do not pred ict altered splicing. However, this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Arg1316Arg va riant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
Find out detailed SpliceAI scores and Pangolin per-transcript scores at