chr4-144995386-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001256706.2(ANAPC10):​c.545G>A​(p.Arg182His) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ANAPC10
NM_001256706.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37518466).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANAPC10NM_001256706.2 linkc.545G>A p.Arg182His missense_variant Exon 5 of 5 ENST00000507656.6 NP_001243635.1 Q9UM13

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANAPC10ENST00000507656.6 linkc.545G>A p.Arg182His missense_variant Exon 5 of 5 1 NM_001256706.2 ENSP00000423995.1 Q9UM13
ENSG00000285713ENST00000649263.1 linkn.327+69186G>A intron_variant Intron 4 of 8 ENSP00000497507.1 A0A3B3ISY7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1454990
Hom.:
0
Cov.:
29
AF XY:
0.00000414
AC XY:
3
AN XY:
724238
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:
0.00000452
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.545G>A (p.R182H) alteration is located in exon 5 (coding exon 4) of the ANAPC10 gene. This alteration results from a G to A substitution at nucleotide position 545, causing the arginine (R) at amino acid position 182 to be replaced by a histidine (H). 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
0.22
BayesDel_addAF
Uncertain
0.039
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.071
T;T;T;T
Eigen
Benign
0.084
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.77
T;.;.;.
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.38
T;T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.46
N;N;N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.76
.;N;N;N
REVEL
Benign
0.23
Sift
Benign
0.17
.;T;T;T
Sift4G
Uncertain
0.023
D;D;D;D
Polyphen
0.0010
B;B;B;B
Vest4
0.48
MutPred
0.63
Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);Loss of MoRF binding (P = 4e-04);
MVP
0.82
MPC
0.40
ClinPred
0.91
D
GERP RS
5.6
Varity_R
0.29
gMVP
0.53

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.

Other links and lift over

dbSNP: rs1731459048; hg19: chr4-145916538; COSMIC: COSV58739104; COSMIC: COSV58739104; API