rs577534147
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001039141.3(TRIOBP):c.6575+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,600,954 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 4 hom. )
Consequence
TRIOBP
NM_001039141.3 intron
NM_001039141.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.38
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 22-37768190-G-A is Benign according to our data. Variant chr22-37768190-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 228041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000171 (26/152268) while in subpopulation SAS AF= 0.00456 (22/4828). AF 95% confidence interval is 0.00308. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.6575+14G>A | intron_variant | ENST00000644935.1 | |||
TRIOBP | NM_007032.5 | c.1436+14G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.6575+14G>A | intron_variant | NM_001039141.3 | A2 | ||||
TRIOBP | ENST00000403663.6 | c.1436+14G>A | intron_variant | 1 | P2 | ||||
TRIOBP | ENST00000344404.10 | c.*6058+14G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000582 AC: 134AN: 230284Hom.: 1 AF XY: 0.000769 AC XY: 96AN XY: 124778
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GnomAD4 exome AF: 0.000276 AC: 400AN: 1448686Hom.: 4 Cov.: 31 AF XY: 0.000403 AC XY: 290AN XY: 719952
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 26, 2015 | c.6575+14G>A in intron 19 of TRIOBP: This variant is not expected to have clinic al significance because it has been identified in 0.6% (69/11848) of South Asian chromosomes including 1 homozygote by the Exome Aggregation Consortium (ExAC, h ttp://exac.broadinstitute.org) - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 18, 2023 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at