rs35765596

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-36396387-C-A
• chr7-36396387-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANLN	NM_018685.5	c.140C>A	p.Ala47Glu	missense_variant	Exon 2 of 24	ENST00000265748.7	NP_061155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANLN	ENST00000265748.7	c.140C>A	p.Ala47Glu	missense_variant	Exon 2 of 24	1	NM_018685.5	ENSP00000265748.2
ANLN	ENST00000396068.6	c.140C>A	p.Ala47Glu	missense_variant	Exon 2 of 23	1		ENSP00000379380.2
ANLN	ENST00000424865.1	c.74C>A	p.Ala25Glu	missense_variant	Exon 2 of 4	3		ENSP00000404979.1
ANLN	ENST00000418118.1	c.74C>A	p.Ala25Glu	missense_variant	Exon 2 of 2	3		ENSP00000406584.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.8	M;M;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.9	N;N;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Benign	0.34	T;T;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.40
MutPred		0.13		Loss of MoRF binding (P = 0.0387);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-36435996;