Variant chr7-36396312-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000265748.7(ANLN):c.65A>G(p.Lys22Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANLN
ENST00000265748.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66

Variant links:

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]

ANLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANLN	NM_018685.5 linkuse as main transcript	c.65A>G	p.Lys22Arg	missense_variant	2/24	ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7 linkuse as main transcript	c.65A>G	p.Lys22Arg	missense_variant	2/24	1	NM_018685.5	ENSP00000265748	P2	Q9NQW6-1
ANLN	ENST00000396068.6 linkuse as main transcript	c.65A>G	p.Lys22Arg	missense_variant	2/23	1		ENSP00000379380	A2	Q9NQW6-2
ANLN	ENST00000418118.1 linkuse as main transcript	c.-2A>G		5_prime_UTR_variant	2/2	3		ENSP00000406584
ANLN	ENST00000424865.1 linkuse as main transcript	c.-2A>G		5_prime_UTR_variant	2/4	3		ENSP00000404979

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723868

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Focal segmental glomerulosclerosis 8

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Neuberg Centre For Genomic Medicine, NCGM

The missense variant p.K22R in ANLN (NM_018685.5) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.K22R variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.K22R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The lysine residue at codon 22 of ANLN is conserved in all mammalian species. The nucleotide c.65 in ANLN is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

2.9

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.044

D;D

Polyphen

1.0

D;D

Vest4

0.54

MutPred

0.20

Loss of glycosylation at K22 (P = 0.0439);Loss of glycosylation at K22 (P = 0.0439);

MVP

0.75

MPC

0.53

ClinPred

0.99

GERP RS

5.7

Varity_R

0.54

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over