Variant chr7-36396414-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000265748.7(ANLN):c.167G>A(p.Gly56Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,419,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANLN
ENST00000265748.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09877607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANLN	NM_018685.5 linkuse as main transcript	c.167G>A	p.Gly56Asp	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.167G>A	p.Gly56Asp	missense_variant	2/24	1	NM_018685.5	ENSP00000265748	P2	Q9NQW6-1
ANLN	ENST00000396068.6 linkuse as main transcript	c.167G>A	p.Gly56Asp	missense_variant	2/23	1		ENSP00000379380	A2	Q9NQW6-2
ANLN	ENST00000424865.1 linkuse as main transcript	c.101G>A	p.Gly34Asp	missense_variant	2/4	3		ENSP00000404979
ANLN	ENST00000418118.1 linkuse as main transcript	c.101G>A	p.Gly34Asp	missense_variant	2/2	3		ENSP00000406584

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000851

AC:

AN:

235020

Hom.:

AF XY:

0.00000787

AC XY:

AN XY:

127054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000669

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:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1419622

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703526

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000494

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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 19, 2022

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. 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 tolerated. This variant has not been reported in the literature in individuals affected with ANLN-related conditions. This variant is present in population databases (rs752908729, gnomAD 0.007%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 56 of the ANLN protein (p.Gly56Asp). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.035

T;.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.0

N;N;N;D

REVEL

Benign

0.11

Sift

Benign

0.42

T;T;T;D

Sift4G

Benign

0.52

T;T;D;D

Polyphen

0.0010

B;B;.;.

Vest4

0.21

MutPred

0.069

Loss of catalytic residue at P52 (P = 0.0914);Loss of catalytic residue at P52 (P = 0.0914);.;.;

MVP

0.55

MPC

0.18

ClinPred

0.093

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.054

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