rs201529268
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001039141.3(TRIOBP):c.6324+162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,329,812 control chromosomes in the GnomAD database, including 2 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: 33)
Exomes 𝑓: 0.00030 ( 2 hom. )
Consequence
TRIOBP
NM_001039141.3 intron
NM_001039141.3 intron
Scores
15
Clinical Significance
Conservation
PhyloP100: -1.20
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0043849945).
BP6
Variant 22-37759426-G-A is Benign according to our data. Variant chr22-37759426-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165606.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-37759426-G-A is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.6324+162G>A | intron_variant | ENST00000644935.1 | NP_001034230.1 | |||
TRIOBP | NM_138632.2 | c.1195G>A | p.Val399Met | missense_variant | 8/8 | NP_619538.2 | ||
TRIOBP | NM_007032.5 | c.1185+162G>A | intron_variant | NP_008963.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000407319.7 | c.1195G>A | p.Val399Met | missense_variant | 8/8 | 1 | ENSP00000383913 | |||
TRIOBP | ENST00000644935.1 | c.6324+162G>A | intron_variant | NM_001039141.3 | ENSP00000496394 | A2 | ||||
TRIOBP | ENST00000403663.6 | c.1185+162G>A | intron_variant | 1 | ENSP00000386026 | P2 | ||||
TRIOBP | ENST00000344404.10 | c.*5807+162G>A | intron_variant, NMD_transcript_variant | 2 | ENSP00000340312 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000466 AC: 116AN: 249068Hom.: 1 AF XY: 0.000408 AC XY: 55AN XY: 134832
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GnomAD4 exome AF: 0.000297 AC: 350AN: 1177506Hom.: 2 Cov.: 17 AF XY: 0.000249 AC XY: 149AN XY: 599226
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GnomAD4 genome AF: 0.000171 AC: 26AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74488
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
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 | Nov 17, 2016 | p.Val339Met in exon 17A of TRIOBP: This variant is not expected to have clinical significance because it has been identified in 0.3% (38/11576) of Latino chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201529268). - |
TRIOBP-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 01, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Vest4
MVP
ClinPred
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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