5-893075-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_004237.4(TRIP13):c.77A>G(p.His26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,444,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 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_004237.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIP13 | NM_004237.4 | c.77A>G | p.His26Arg | missense_variant | Exon 1 of 13 | ENST00000166345.8 | NP_004228.1 | |
TRIP13 | NM_001166260.2 | c.77A>G | p.His26Arg | missense_variant | Exon 1 of 9 | NP_001159732.1 | ||
TRIP13 | XM_011514163.2 | c.77A>G | p.His26Arg | missense_variant | Exon 1 of 14 | XP_011512465.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIP13 | ENST00000166345.8 | c.77A>G | p.His26Arg | missense_variant | Exon 1 of 13 | 1 | NM_004237.4 | ENSP00000166345.3 | ||
TRIP13 | ENST00000512024.5 | n.192A>G | non_coding_transcript_exon_variant | Exon 1 of 9 | 1 | |||||
TRIP13 | ENST00000508456.1 | n.51A>G | non_coding_transcript_exon_variant | Exon 1 of 3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000919 AC: 2AN: 217592Hom.: 0 AF XY: 0.00000836 AC XY: 1AN XY: 119632
GnomAD4 exome AF: 0.00000485 AC: 7AN: 1444434Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3AN XY: 717804
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 3;C5436599:Oocyte maturation defect 9 Pathogenic:1
PM2_Supporting+PP3+PM3+PP1+PP4 -
Oocyte maturation defect 9 Pathogenic:1
- -
not provided Uncertain:1
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 26 of the TRIP13 protein (p.His26Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with female infertility (PMID: 32473092, 35812326, 37340965). ClinVar contains an entry for this variant (Variation ID: 977641). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects TRIP13 function (PMID: 35812326, 37340965). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at