Variant 7-36396327-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018685.5(ANLN):c.80C>T(p.Pro27Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000481 in 1,456,160 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 1 hom. )

Consequence

ANLN
NM_018685.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.50

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANLN	NM_018685.5 link	c.80C>T	p.Pro27Leu	missense_variant	2/24	ENST00000265748.7	NP_061155.2	Q9NQW6-1A0A024RA49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANLN	ENST00000265748.7 link	c.80C>T	p.Pro27Leu	missense_variant	2/24	1	NM_018685.5	ENSP00000265748.2	Q9NQW6-1
ANLN	ENST00000396068.6 link	c.80C>T	p.Pro27Leu	missense_variant	2/23	1		ENSP00000379380.2	Q9NQW6-2
ANLN	ENST00000424865.1 link	c.14C>T	p.Pro5Leu	missense_variant	2/4	3		ENSP00000404979.1	C9JJT6
ANLN	ENST00000418118.1 link	c.14C>T	p.Pro5Leu	missense_variant	2/2	3		ENSP00000406584.1	C9J0G4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250616

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1456160

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724462

show subpopulations

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:

0.0000583

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 24, 2023

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 27 of the ANLN protein (p.Pro27Leu). This variant is present in population databases (rs765537134, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ANLN-related conditions. 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 disruptive. 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-0.29

MutationAssessor

Pathogenic

3.0

M;M;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.3

D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.66

MutPred

0.29

Loss of glycosylation at T28 (P = 0.0469);Loss of glycosylation at T28 (P = 0.0469);.;.;

MVP

0.71

MPC

0.60

ClinPred

0.98

GERP RS

5.7

Varity_R

0.43

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over