rs587777741
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PP3_ModeratePP5_Very_StrongBS2_Supporting
The NM_018685.5(ANLN):c.1291C>T(p.Arg431Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000393 in 1,603,632 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 Likely pathogenic (★★).
Frequency
Consequence
NM_018685.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANLN | NM_018685.5 | c.1291C>T | p.Arg431Cys | missense_variant | Exon 7 of 24 | ENST00000265748.7 | NP_061155.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152004Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000166 AC: 4AN: 241526Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130724
GnomAD4 exome AF: 0.0000400 AC: 58AN: 1451628Hom.: 0 Cov.: 30 AF XY: 0.0000374 AC XY: 27AN XY: 722142
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74232
ClinVar
Submissions by phenotype
Focal segmental glomerulosclerosis 8 Pathogenic:2
- -
ACMG codes: PS3, PP1_Strong, PP3 -
not provided Pathogenic:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 431 of the ANLN protein (p.Arg431Cys). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individuals with focal segmental glomerulosclerosis and/or steroid resistant nephrotic syndrome (PMID: 24676636, 30406062). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 156221). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ANLN protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ANLN function (PMID: 24676636). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at