2-27055171-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_021831.6(AGBL5):c.826C>T(p.Arg276Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R276P) has been classified as Uncertain significance.
Frequency
Consequence
NM_021831.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGBL5 | NM_021831.6 | c.826C>T | p.Arg276Trp | missense_variant | 6/15 | ENST00000360131.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGBL5 | ENST00000360131.5 | c.826C>T | p.Arg276Trp | missense_variant | 6/15 | 1 | NM_021831.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 276 of the AGBL5 protein (p.Arg276Trp). This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 242933). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 26355662). It has also been observed to segregate with disease in related individuals. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | AGBL5: PM2, PM3, PP1:Moderate - |
Retinitis pigmentosa 75 Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Feb 11, 2020 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 06, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at