rs587777741
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PP3_ModeratePP5_ModerateBS2_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 Pathogenic (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
ANLN
NM_018685.5 missense
NM_018685.5 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 3.90
Genes affected
ANLN (HGNC:14082): (anillin, actin binding protein) This gene encodes an actin-binding protein that plays a role in cell growth and migration, and in cytokinesis. The encoded protein is thought to regulate actin cytoskeletal dynamics in podocytes, components of the glomerulus. Mutations in this gene are associated with focal segmental glomerulosclerosis 8. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.841
PP5
Variant 7-36411062-C-T is Pathogenic according to our data. Variant chr7-36411062-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 156221.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANLN | NM_018685.5 | c.1291C>T | p.Arg431Cys | missense_variant | 7/24 | ENST00000265748.7 | NP_061155.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANLN | ENST00000265748.7 | c.1291C>T | p.Arg431Cys | missense_variant | 7/24 | 1 | NM_018685.5 | ENSP00000265748.2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152004Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000166 AC: 4AN: 241526Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130724
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GnomAD4 exome AF: 0.0000400 AC: 58AN: 1451628Hom.: 0 Cov.: 30 AF XY: 0.0000374 AC XY: 27AN XY: 722142
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74232
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Focal segmental glomerulosclerosis 8 Pathogenic:2
Pathogenic, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Sep 26, 2022 | ACMG codes: PS3, PP1_Strong, PP3 - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at