22-37772696-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001039141.3(TRIOBP):c.7032G>A(p.Glu2344=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,614,100 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0058 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 10 hom. )
Consequence
TRIOBP
NM_001039141.3 synonymous
NM_001039141.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.219
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 22-37772696-G-A is Benign according to our data. Variant chr22-37772696-G-A is described in ClinVar as [Benign]. Clinvar id is 227129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37772696-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.219 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00577 (879/152300) while in subpopulation AFR AF= 0.0199 (827/41552). AF 95% confidence interval is 0.0188. There are 6 homozygotes in gnomad4. There are 423 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.7032G>A | p.Glu2344= | synonymous_variant | 23/24 | ENST00000644935.1 | |
TRIOBP | NM_007032.5 | c.1893G>A | p.Glu631= | synonymous_variant | 13/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.7032G>A | p.Glu2344= | synonymous_variant | 23/24 | NM_001039141.3 | A2 | ||
TRIOBP | ENST00000403663.6 | c.1893G>A | p.Glu631= | synonymous_variant | 13/14 | 1 | P2 | ||
TRIOBP | ENST00000344404.10 | c.*6515G>A | 3_prime_UTR_variant, NMD_transcript_variant | 21/22 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00575 AC: 875AN: 152182Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00133 AC: 331AN: 249442Hom.: 1 AF XY: 0.00101 AC XY: 137AN XY: 135338
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GnomAD4 exome AF: 0.000606 AC: 886AN: 1461800Hom.: 10 Cov.: 32 AF XY: 0.000540 AC XY: 393AN XY: 727202
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GnomAD4 genome AF: 0.00577 AC: 879AN: 152300Hom.: 6 Cov.: 32 AF XY: 0.00568 AC XY: 423AN XY: 74484
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Glu2344Glu in Exon 23 of TRIOBP: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 1.8% (67/3684) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs61737839). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at