Variant 4-25406881-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013367.3(ANAPC4):c.1370A>G(p.Asn457Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000035 in 1,599,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

ANAPC4
NM_013367.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

Variant links:

Genes affected

ANAPC4 (HGNC:19990): (anaphase promoting complex subunit 4) A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ANAPC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.22558856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANAPC4	NM_013367.3 linkuse as main transcript	c.1370A>G	p.Asn457Ser	missense_variant	19/29	ENST00000315368.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANAPC4	ENST00000315368.8 linkuse as main transcript	c.1370A>G	p.Asn457Ser	missense_variant	19/29	1	NM_013367.3	P4	Q9UJX5-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000332

AC:

AN:

1447386

Hom.:

Cov.:

AF XY:

0.0000431

AC XY:

AN XY:

719678

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000389

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0000529

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 08, 2023

The c.1370A>G (p.N457S) alteration is located in exon 19 (coding exon 18) of the ANAPC4 gene. This alteration results from a A to G substitution at nucleotide position 1370, causing the asparagine (N) at amino acid position 457 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.092

Sift

Benign

0.22

T;T

Sift4G

Benign

0.76

T;T

Polyphen

0.029

B;.

Vest4

0.26

MutPred

0.48

Gain of relative solvent accessibility (P = 0.0215);.;

MVP

0.45

MPC

0.43

ClinPred

0.68

GERP RS

5.5

Varity_R

0.18

gMVP

0.059

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