7-36406247-G-C

Variant names:

• chr7-36406247-G-C
• rs197367
• NM_018685.5:c.554G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018685.5(ANLN):​c.554G>C​(p.Arg185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. R185K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANLN NM_018685.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 32 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0552139).

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.554G>C	p.Arg185Thr	missense	Exon 4 of 24	NP_061155.2
	ANLN	NM_001284301.3		c.554G>C	p.Arg185Thr	missense	Exon 4 of 23	NP_001271230.1	Q9NQW6-2
	ANLN	NM_001284302.3		c.554G>C	p.Arg185Thr	missense	Exon 4 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.554G>C	p.Arg185Thr	missense	Exon 4 of 24	ENSP00000265748.2	Q9NQW6-1
	ANLN	ENST00000396068.6	TSL:1	c.554G>C	p.Arg185Thr	missense	Exon 4 of 23	ENSP00000379380.2	Q9NQW6-2
	ANLN	ENST00000918505.1		c.554G>C	p.Arg185Thr	missense	Exon 4 of 26	ENSP00000588564.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.67
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.039
Sift	Benign	0.20	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.15		Gain of glycosylation at R185 (P = 7e-04)
MVP		0.22
MPC		0.19
ClinPred		0.089	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.16
Mutation Taster		=91/9	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: rs197367; hg19: chr7-36445856;