NM_018685.5:c.116G>A

Variant names:

• chr7-36396363-G-A
• rs555242135
• NM_018685.5:c.116G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_018685.5(ANLN):​c.116G>A​(p.Arg39Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,604,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ANLN NM_018685.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 8.21
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 8

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2561113).
• BS2: High AC in GnomAdExome4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018685.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	NM_018685.5	MANE Select	c.116G>A	p.Arg39Gln	missense	Exon 2 of 24	NP_061155.2
	ANLN	NM_001284301.3		c.116G>A	p.Arg39Gln	missense	Exon 2 of 23	NP_001271230.1	Q9NQW6-2
	ANLN	NM_001284302.3		c.116G>A	p.Arg39Gln	missense	Exon 2 of 23	NP_001271231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANLN	ENST00000265748.7	TSL:1 MANE Select	c.116G>A	p.Arg39Gln	missense	Exon 2 of 24	ENSP00000265748.2	Q9NQW6-1
	ANLN	ENST00000396068.6	TSL:1	c.116G>A	p.Arg39Gln	missense	Exon 2 of 23	ENSP00000379380.2	Q9NQW6-2
	ANLN	ENST00000918505.1		c.116G>A	p.Arg39Gln	missense	Exon 2 of 26	ENSP00000588564.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250694 AF XY: 0.0000295

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000165 AC: 24 AN: 1452352 Hom.: 0 Cov.: 30 AF XY: 0.0000166 AC XY: 12 AN XY: 721690

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.0000224 AC: 1 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25884

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.000210 AC: 18 AN: 85548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104698

Other (OTH) AF: 0.0000501 AC: 3 AN: 59870

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74492

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000576 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0032	T
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		8.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.17		Gain of ubiquitination at K38 (P = 0.02)
MVP		0.79
MPC		0.63
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.46
gMVP		0.38
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs555242135; hg19: chr7-36435972;