Variant 3-134482880-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015391.4(ANAPC13):c.25G>A(p.Gly9Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000451 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ANAPC13
NM_015391.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.85

Variant links:

Genes affected

ANAPC13 (HGNC:24540): (anaphase promoting complex subunit 13) This gene encodes a component of the anaphase promoting complex, a large ubiquitin-protein ligase that controls cell cycle progression by regulating the degradation of cell cycle regulators such as B-type cyclins. The encoded protein is evolutionarily conserved and is required for the integrity and ubiquitin ligase activity of the anaphase promoting complex. Pseudogenes and splice variants have been found for this gene; however, the biological validity of some of the splice variants has not been determined. [provided by RefSeq, Nov 2008]

ANAPC13 links:

ANAPC13 (HGNC:):

ANAPC13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC13	NM_015391.4 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	2/3	ENST00000354910.10	NP_056206.1	Q9BS18A8K3Z6
ANAPC13	NM_001242374.1 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	2/3		NP_001229303.1	Q9BS18A8K3Z6
ANAPC13	NM_001242375.1 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	2/3		NP_001229304.1	Q9BS18A8K3Z6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC13	ENST00000354910.10 linkuse as main transcript	c.25G>A	p.Gly9Arg	missense_variant	2/3	1	NM_015391.4	ENSP00000346987.5		Q9BS18

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251482

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000451

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727230

show subpopulations

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:

0.0000936

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.25G>A (p.G9R) alteration is located in exon 2 (coding exon 1) of the ANAPC13 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the glycine (G) at amino acid position 9 to be replaced by an arginine (R). 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

0.96

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.40

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

T;T;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;.;.;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.83

D;D;D;D

MetaSVM

Benign

-0.76

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-6.9

D;D;D;D

REVEL

Pathogenic

0.70

Sift

Benign

0.067

T;T;T;T

Sift4G

Benign

0.098

T;T;T;T

Polyphen

0.58

P;P;P;P

Vest4

0.95

MutPred

0.69

Gain of disorder (P = 0.0184);Gain of disorder (P = 0.0184);Gain of disorder (P = 0.0184);Gain of disorder (P = 0.0184);

MVP

0.40

MPC

0.074

ClinPred

0.36

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over