7-36396283-C-A

Variant names:

• chr7-36396283-C-A
• rs762482968
• NM_018685.5:c.36C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018685.5(ANLN):​c.36C>A​(p.Thr12Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,100 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. Synonymous variant affecting the same amino acid position (i.e. T12T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANLN NM_018685.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• 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: 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=-0.792 with no splicing effect.

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.36C>A	p.Thr12Thr	synonymous	Exon 2 of 24	NP_061155.2
	ANLN	NM_001284301.3		c.36C>A	p.Thr12Thr	synonymous	Exon 2 of 23	NP_001271230.1	Q9NQW6-2
	ANLN	NM_001284302.3		c.36C>A	p.Thr12Thr	synonymous	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.36C>A	p.Thr12Thr	synonymous	Exon 2 of 24	ENSP00000265748.2	Q9NQW6-1
	ANLN	ENST00000396068.6	TSL:1	c.36C>A	p.Thr12Thr	synonymous	Exon 2 of 23	ENSP00000379380.2	Q9NQW6-2
	ANLN	ENST00000918505.1		c.36C>A	p.Thr12Thr	synonymous	Exon 2 of 26	ENSP00000588564.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451100 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721630

African (AFR) AF: 0.00 AC: 0 AN: 33222

American (AMR) AF: 0.00 AC: 0 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.00 AC: 0 AN: 85102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104804

Other (OTH) AF: 0.00 AC: 0 AN: 59820

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.1
DANN	Benign	0.83
PhyloP100		-0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs762482968; hg19: chr7-36435892;