7-36396390-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018685.5(ANLN):c.143G>A(p.Ser48Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,595,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ANLN
NM_018685.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.05

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005140722).

BP6

Variant 7-36396390-G-A is Benign according to our data. Variant chr7-36396390-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1166530.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd at 178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANLN	NM_018685.5 linkuse as main transcript	c.143G>A	p.Ser48Asn	missense_variant	2/24	ENST00000265748.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANLN	ENST00000265748.7 linkuse as main transcript	c.143G>A	p.Ser48Asn	missense_variant	2/24	1	NM_018685.5	P2	Q9NQW6-1
ANLN	ENST00000396068.6 linkuse as main transcript	c.143G>A	p.Ser48Asn	missense_variant	2/23	1		A2	Q9NQW6-2
ANLN	ENST00000424865.1 linkuse as main transcript	c.77G>A	p.Ser26Asn	missense_variant	2/4	3
ANLN	ENST00000418118.1 linkuse as main transcript	c.77G>A	p.Ser26Asn	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000329

AC:

AN:

248986

Hom.:

AF XY:

0.000260

AC XY:

AN XY:

134582

show subpopulations

Gnomad AFR exome

AF:

0.00489

Gnomad AMR exome

AF:

0.0000887

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:

0.000127

AC:

184

AN:

1443534

Hom.:

Cov.:

AF XY:

0.0000907

AC XY:

AN XY:

716510

show subpopulations

Gnomad4 AFR exome

AF:

0.00518

Gnomad4 AMR exome

AF:

0.0000678

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:

0.00000182

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152278

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00411

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.00142

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 20, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Oct 20, 2022	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.79

DEOGEN2

Benign

0.053

T;.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0051

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

0.83

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.65

N;N;N;D

REVEL

Benign

0.13

Sift

Benign

0.81

T;T;T;T

Sift4G

Benign

0.76

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.16

MVP

0.43

MPC

0.12

ClinPred

0.0052

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.10

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