chr22-37710514-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001039141.3(TRIOBP):āc.202A>Gā(p.Thr68Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,611,602 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T68I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001039141.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.202A>G | p.Thr68Ala | missense_variant | 4/24 | ENST00000644935.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.202A>G | p.Thr68Ala | missense_variant | 4/24 | NM_001039141.3 | A2 | ||
TRIOBP | ENST00000492485.5 | n.338A>G | non_coding_transcript_exon_variant | 3/5 | 1 | ||||
TRIOBP | ENST00000344404.10 | c.202A>G | p.Thr68Ala | missense_variant, NMD_transcript_variant | 3/22 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000552 AC: 84AN: 152042Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000341 AC: 83AN: 243210Hom.: 0 AF XY: 0.000309 AC XY: 41AN XY: 132642
GnomAD4 exome AF: 0.000286 AC: 417AN: 1459442Hom.: 0 Cov.: 32 AF XY: 0.000273 AC XY: 198AN XY: 726052
GnomAD4 genome AF: 0.000552 AC: 84AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.000632 AC XY: 47AN XY: 74384
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 68 of the TRIOBP protein (p.Thr68Ala). This variant is present in population databases (rs200529550, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with TRIOBP-related conditions. ClinVar contains an entry for this variant (Variation ID: 43849). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 28, 2015 | p.Thr68Ala in exon 4 of TRIOBP: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, 8 mammals have an alanine (Ala) at this position despite high nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. It has also been identified in 0.2% ( 17/8836) of African chromosomes by the Exome Aggregation Consortium (ExAC, http: //exac.broadinstitute.org; dbSNP rs200529550). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at