7-36396387-C-A

Variant names:

• chr7-36396387-C-A
• rs35765596
• NM_018685.5:c.140C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018685.5(ANLN):​c.140C>A​(p.Ala47Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,444,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A47G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANLN NM_018685.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23824048).

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.140C>A	p.Ala47Glu	missense	Exon 2 of 24	NP_061155.2
	ANLN	NM_001284301.3		c.140C>A	p.Ala47Glu	missense	Exon 2 of 23	NP_001271230.1	Q9NQW6-2
	ANLN	NM_001284302.3		c.140C>A	p.Ala47Glu	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.140C>A	p.Ala47Glu	missense	Exon 2 of 24	ENSP00000265748.2	Q9NQW6-1
	ANLN	ENST00000396068.6	TSL:1	c.140C>A	p.Ala47Glu	missense	Exon 2 of 23	ENSP00000379380.2	Q9NQW6-2
	ANLN	ENST00000918505.1		c.140C>A	p.Ala47Glu	missense	Exon 2 of 26	ENSP00000588564.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1444016 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 716688

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33234

American (AMR) AF: 0.00 AC: 0 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25734

East Asian (EAS) AF: 0.00 AC: 0 AN: 39348

South Asian (SAS) AF: 0.00 AC: 0 AN: 84694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098672

Other (OTH) AF: 0.00 AC: 0 AN: 59382

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.5
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.34	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.13		Loss of MoRF binding (P = 0.0387)
MVP		0.49
MPC		0.64
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.17
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs35765596; hg19: chr7-36435996;