rs1731459048

Variant names:

• chr4-144995386-C-T
• rs1731459048
• NM_001256706.2:c.545G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 0 publications found

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]

ENSG00000285713 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256706.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC10	NM_001256706.2	MANE Select	c.545G>A	p.Arg182His	missense	Exon 5 of 5	NP_001243635.1	Q9UM13
	ANAPC10	NM_001318367.2		c.647G>A	p.Arg216His	missense	Exon 5 of 5	NP_001305296.1
	ANAPC10	NM_001256709.2		c.578G>A	p.Arg193His	missense	Exon 7 of 7	NP_001243638.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC10	ENST00000507656.6	TSL:1 MANE Select	c.545G>A	p.Arg182His	missense	Exon 5 of 5	ENSP00000423995.1	Q9UM13
	ANAPC10	ENST00000309439.9	TSL:1	c.545G>A	p.Arg182His	missense	Exon 5 of 5	ENSP00000310071.5	Q9UM13
	ANAPC10	ENST00000451299.6	TSL:1	c.545G>A	p.Arg182His	missense	Exon 6 of 6	ENSP00000403891.2	Q9UM13

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

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 85602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1106934

Other (OTH) AF: 0.00 AC: 0 AN: 60174

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.46	N
PhyloP100		6.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.23
Sift	Benign	0.17	T
Sift4G	Uncertain	0.023	D
Polyphen		0.0010	B
Vest4		0.48
MutPred		0.63		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
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

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