22-37757932-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001039141.3(TRIOBP):c.6007G>A(p.Gly2003Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,556,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001039141.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.6007G>A | p.Gly2003Ser | missense_variant | 16/24 | ENST00000644935.1 | NP_001034230.1 | |
TRIOBP | NM_007032.5 | c.868G>A | p.Gly290Ser | missense_variant | 6/14 | NP_008963.3 | ||
TRIOBP | NM_138632.2 | c.868G>A | p.Gly290Ser | missense_variant | 6/8 | NP_619538.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.6007G>A | p.Gly2003Ser | missense_variant | 16/24 | NM_001039141.3 | ENSP00000496394 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000435 AC: 7AN: 160834Hom.: 0 AF XY: 0.0000233 AC XY: 2AN XY: 85846
GnomAD4 exome AF: 0.0000207 AC: 29AN: 1403820Hom.: 0 Cov.: 32 AF XY: 0.0000159 AC XY: 11AN XY: 693108
GnomAD4 genome AF: 0.000197 AC: 30AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 10, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2003 of the TRIOBP protein (p.Gly2003Ser). This variant is present in population databases (rs397516554, gnomAD 0.04%). 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: 43863). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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. - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2023 | The c.6007G>A (p.G2003S) alteration is located in exon 16 (coding exon 14) of the TRIOBP gene. This alteration results from a G to A substitution at nucleotide position 6007, causing the glycine (G) at amino acid position 2003 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 29, 2013 | Gly2003Ser in exon 16 of TRIOBP: This variant is not expected to have clinical significance because glycine (Gly) at position 2003 is not conserved across mamm als and several species, including pika and opposum, carry a serine (Ser) at th is position. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at