rs727503526
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The ENST00000407319.7(TRIOBP):āc.1227A>Gā(p.Pro409=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,504,548 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 Likely benign (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 33)
Exomes š: 0.000040 ( 0 hom. )
Consequence
TRIOBP
ENST00000407319.7 synonymous
ENST00000407319.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.14
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 22-37759458-A-G is Benign according to our data. Variant chr22-37759458-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 165607.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-37759458-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.14 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.6324+194A>G | intron_variant | ENST00000644935.1 | |||
TRIOBP | NM_138632.2 | c.1227A>G | p.Pro409= | synonymous_variant | 8/8 | ||
TRIOBP | NM_007032.5 | c.1185+194A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000407319.7 | c.1227A>G | p.Pro409= | synonymous_variant | 8/8 | 1 | |||
TRIOBP | ENST00000644935.1 | c.6324+194A>G | intron_variant | NM_001039141.3 | A2 | ||||
TRIOBP | ENST00000403663.6 | c.1185+194A>G | intron_variant | 1 | P2 | ||||
TRIOBP | ENST00000344404.10 | c.*5807+194A>G | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152154Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000197 AC: 49AN: 248738Hom.: 0 AF XY: 0.000171 AC XY: 23AN XY: 134700
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GnomAD4 exome AF: 0.0000399 AC: 54AN: 1352394Hom.: 0 Cov.: 22 AF XY: 0.0000383 AC XY: 26AN XY: 678918
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74322
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
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 | Jun 30, 2014 | Pro409Pro in exon 17A of TRIOBP: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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