NM_018685.5:c.44G>C

Variant names:

• chr7-36396291-G-C
• NM_018685.5:c.44G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018685.5(ANLN):​c.44G>C​(p.Arg15Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANLN NM_018685.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.21

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANLN	NM_018685.5	c.44G>C	p.Arg15Thr	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.44G>C	p.Arg15Thr	missense_variant	Exon 2 of 24	1	NM_018685.5	ENSP00000265748.2
ANLN	ENST00000396068.6	c.44G>C	p.Arg15Thr	missense_variant	Exon 2 of 23	1		ENSP00000379380.2
ANLN	ENST00000424865	c.-23G>C		5_prime_UTR_variant	Exon 2 of 4	3		ENSP00000404979.1
ANLN	ENST00000418118.1	c.-23G>C		5_prime_UTR_variant	Exon 2 of 2	3		ENSP00000406584.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44G>C (p.R15T) alteration is located in exon 2 (coding exon 2) of the ANLN gene. This alteration results from a G to C substitution at nucleotide position 44, causing the arginine (R) at amino acid position 15 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		1.0	D;D
Vest4		0.88
MutPred		0.34		Gain of phosphorylation at R15 (P = 0.0065);Gain of phosphorylation at R15 (P = 0.0065);
MVP		0.75
MPC		0.71
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.40

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: chr7-36435900;