7-36396285-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3 BP4_Strong BP6_Moderate BS2

The NM_018685.5(ANLN):c.38G>A(p.Arg13His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,605,254 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (2 hom.)
• Consequence: ANLN NM_018685.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.21

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PrimateAI [when BayesDel_addAF, BayesDel_noAF, max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.051848143).
• BP6: Variant 7-36396285-G-A is Benign according to our data. Variant chr7-36396285-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2897844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANLN	NM_018685.5	c.38G>A	p.Arg13His	missense_variant	2/24	ENST00000265748.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANLN	ENST00000265748.7	c.38G>A	p.Arg13His	missense_variant	2/24	1	NM_018685.5	P2
ANLN	ENST00000396068.6	c.38G>A	p.Arg13His	missense_variant	2/23	1		A2
ANLN	ENST00000418118.1	c.-29G>A		5_prime_UTR_variant	2/2	3
ANLN	ENST00000424865.1	c.-29G>A		5_prime_UTR_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000341 AC: 85 AN: 249624 Hom.: 0 AF XY: 0.000304 AC XY: 41 AN XY: 134910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.0000660

Gnomad FIN exome AF: 0.00328

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000154 AC: 224 AN: 1452994 Hom.: 2 Cov.: 30 AF XY: 0.000163 AC XY: 118 AN XY: 722616

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.0000937

Gnomad4 FIN exome AF: 0.00305

Gnomad4 NFE exome AF: 0.0000335

Gnomad4 OTH exome AF: 0.000200

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74466

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000343 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.000239 AC: 29

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.10
Cadd	Pathogenic	33
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.38	T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	2.9	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.76
MVP		0.69
MPC		0.65
ClinPred		0.16	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.30

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

Other links and lift over

dbSNP: rs191463158; hg19: chr7-36435894;