rs777449279
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001039141.3(TRIOBP):c.6205G>A(p.Glu2069Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,458,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
TRIOBP
NM_001039141.3 missense
NM_001039141.3 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 4.92
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21209756).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.6205G>A | p.Glu2069Lys | missense_variant | 16/24 | ENST00000644935.1 | |
TRIOBP | NM_007032.5 | c.1066G>A | p.Glu356Lys | missense_variant | 6/14 | ||
TRIOBP | NM_138632.2 | c.1066G>A | p.Glu356Lys | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.6205G>A | p.Glu2069Lys | missense_variant | 16/24 | NM_001039141.3 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000410 AC: 1AN: 243696Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133520
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1458588Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 725578
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
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TwinsUK
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0
ALSPAC
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2
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 | Apr 20, 2015 | The p.Glu2069Lys variant in TRIOBP has not been previously reported in individua ls with hearing loss or in large population studies. Computational prediction to ols and conservation analyses suggest that the variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, the clinical significance of the p.Glu2069Lys variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;.
REVEL
Benign
Sift
Benign
T;.;T;T;.
Sift4G
Benign
T;.;T;T;.
Polyphen
P;P;.;.;.
Vest4
MutPred
Gain of ubiquitination at E2069 (P = 0.0039);Gain of ubiquitination at E2069 (P = 0.0039);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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