chr4-144995437-C-T

Variant names:

• chr4-144995437-C-T
• rs747327271
• NM_001256706.2:c.494G>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.494G>A​(p.Ser165Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANAPC10 NM_001256706.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81
• 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=0.32031524).

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.494G>A	p.Ser165Asn	missense	Exon 5 of 5	NP_001243635.1	Q9UM13
	ANAPC10	NM_001318367.2		c.596G>A	p.Ser199Asn	missense	Exon 5 of 5	NP_001305296.1
	ANAPC10	NM_001256709.2		c.527G>A	p.Ser176Asn	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.494G>A	p.Ser165Asn	missense	Exon 5 of 5	ENSP00000423995.1	Q9UM13
	ANAPC10	ENST00000309439.9	TSL:1	c.494G>A	p.Ser165Asn	missense	Exon 5 of 5	ENSP00000310071.5	Q9UM13
	ANAPC10	ENST00000451299.6	TSL:1	c.494G>A	p.Ser165Asn	missense	Exon 6 of 6	ENSP00000403891.2	Q9UM13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249118 AF XY: 0.00000740

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.061	T
Eigen	Benign	0.052
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.14
Sift	Benign	0.49	T
Sift4G	Benign	0.68	T
Polyphen		0.0030	B
Vest4		0.60
MutPred		0.40		Loss of disorder (P = 0.0842)
MVP		0.79
MPC		0.31
ClinPred		0.39	T
GERP RS		5.8
Varity_R		0.28
gMVP		0.44
Mutation Taster		=41/59	disease causing

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: rs747327271; hg19: chr4-145916589;