chr7-36406247-G-C

Position:

• chr7-36406247-G-C

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANLN	NM_018685.5	c.554G>C	p.Arg185Thr	missense_variant	4/24	ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7	c.554G>C	p.Arg185Thr	missense_variant	4/24	1	NM_018685.5	ENSP00000265748	P2
ANLN	ENST00000396068.6	c.554G>C	p.Arg185Thr	missense_variant	4/23	1		ENSP00000379380	A2
ANLN	ENST00000424865.1	c.488G>C	p.Arg163Thr	missense_variant	4/4	3		ENSP00000404979
ANLN	ENST00000460598.1	n.141G>C		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.20	T;T;D
Sift4G	Benign	0.31	T;T;D
Polyphen		0.0	B;B;.
Vest4		0.13
MutPred		0.15		Gain of glycosylation at R185 (P = 7e-04);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

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: rs197367; hg19: chr7-36445856;