rs150947392
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001039141.3(TRIOBP):c.5767G>A(p.Ala1923Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,585,030 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1923E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001039141.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.5767G>A | p.Ala1923Thr | missense_variant | 16/24 | ENST00000644935.1 | |
TRIOBP | NM_007032.5 | c.628G>A | p.Ala210Thr | missense_variant | 6/14 | ||
TRIOBP | NM_138632.2 | c.628G>A | p.Ala210Thr | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.5767G>A | p.Ala1923Thr | missense_variant | 16/24 | NM_001039141.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000650 AC: 99AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000915 AC: 179AN: 195726Hom.: 5 AF XY: 0.000981 AC XY: 104AN XY: 105978
GnomAD4 exome AF: 0.000498 AC: 713AN: 1432700Hom.: 6 Cov.: 32 AF XY: 0.000596 AC XY: 423AN XY: 710128
GnomAD4 genome ? AF: 0.000650 AC: 99AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000483 AC XY: 36AN XY: 74490
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | TRIOBP: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 06, 2020 | This variant is associated with the following publications: (PMID: 29197352, 28089734, 26969326) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 06, 2017 | p.Ala1923Thr in exon 16 of TRIOBP: This variant is not expected to have clinica l significance because it has been identified in 0.8% (75/9030) of Ashkenazi Jew ish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org; dbSNP rs150947392). In addition, it is not conserved across specie s, including mammals. Of note, bushbaby, mouse, rat, kangaroo rat, and sloth hav e a threonine (Thr) at this position despite high nearby amino acid conservation . - |
TRIOBP-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 20, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at