4-145064606-A-G

Position:

• chr4-145064606-A-G

Variant summary

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

The ENST00000507656.6(ANAPC10):​c.293T>C​(p.Val98Ala) variant causes a missense change involving the alteration of a conserved nucleotide. 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)
• Consequence: ANAPC10 ENST00000507656.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.23

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]

ACMG classification

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	c.293T>C	p.Val98Ala	missense_variant	4/5	ENST00000507656.6	NP_001243635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC10	ENST00000507656.6	c.293T>C	p.Val98Ala	missense_variant	4/5	1	NM_001256706.2	ENSP00000423995	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2024

The c.293T>C (p.V98A) alteration is located in exon 4 (coding exon 3) of the ANAPC10 gene. This alteration results from a T to C substitution at nucleotide position 293, causing the valine (V) at amino acid position 98 to be replaced by an alanine (A). 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	0.28
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	23
DANN	Benign	0.68
DEOGEN2	Benign	0.044	T;T;T;T;.;.;.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.023
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;.;.;.;.;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.48	N;N;N;N;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.25	.;N;N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	1.0	.;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;.;.;T;T
Polyphen		0.022	B;B;B;B;.;.;.;.
Vest4		0.78
MutPred		0.59		Loss of stability (P = 0.0133);Loss of stability (P = 0.0133);Loss of stability (P = 0.0133);Loss of stability (P = 0.0133);Loss of stability (P = 0.0133);Loss of stability (P = 0.0133);Loss of stability (P = 0.0133);Loss of stability (P = 0.0133);
MVP		0.76
MPC		0.43
ClinPred		0.79	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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.

Other links and lift over

hg19: chr4-145985758;