Variant chr4-145081718-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000507656.6(ANAPC10):c.148C>G(p.Leu50Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANAPC10
ENST00000507656.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

Variant links:

Genes affected

ANAPC10 (HGNC:24077): (anaphase promoting complex subunit 10) ANAPC10 is a core subunit of the anaphase-promoting complex (APC), or cyclosome, a ubiquitin protein ligase that is essential for progression through the cell cycle. APC initiates sister chromatid separation by ubiquitinating the anaphase inhibitor securin (PTTG1; MIM 604147) and triggers exit from mitosis by ubiquitinating cyclin B (CCNB1; MIM 123836), the activating subunit of cyclin-dependent kinase-1 (CDK1; MIM 116940) (summary by Wendt et al., 2001 [PubMed 11524682]).[supplied by OMIM, Feb 2011]

ANAPC10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC10	NM_001256706.2 linkuse as main transcript	c.148C>G	p.Leu50Val	missense_variant	3/5	ENST00000507656.6	NP_001243635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC10	ENST00000507656.6 linkuse as main transcript	c.148C>G	p.Leu50Val	missense_variant	3/5	1	NM_001256706.2	ENSP00000423995	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1460682

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726574

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:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 09, 2023

The c.148C>G (p.L50V) alteration is located in exon 3 (coding exon 2) of the ANAPC10 gene. This alteration results from a C to G substitution at nucleotide position 148, causing the leucine (L) at amino acid position 50 to be replaced by a valine (V). 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

Benign

0.18

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

T;T;T;T;.;.;.;T;T

Eigen

Benign

0.018

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;.;.;.;.;D;D;D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.6

L;L;L;L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.1

.;N;N;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.073

.;T;T;T;T;T;T;T;T

Sift4G

Benign

0.19

T;T;T;T;.;.;T;T;.

Polyphen

0.11

B;B;B;B;.;.;.;.;.

Vest4

0.76

MutPred

0.51

Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);Gain of catalytic residue at L50 (P = 0.0416);

MVP

0.77

MPC

0.34

ClinPred

0.75

GERP RS

5.4

Varity_R

0.31

gMVP

0.20

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over