chr3-134482862-T-A

Position:

• chr3-134482862-T-A

Variant summary

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

The NM_015391.4(ANAPC13):​c.43A>T​(p.Ile15Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANAPC13 NM_015391.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

Genes affected

ANAPC13 (HGNC:24540): (anaphase promoting complex subunit 13) This gene encodes a component of the anaphase promoting complex, a large ubiquitin-protein ligase that controls cell cycle progression by regulating the degradation of cell cycle regulators such as B-type cyclins. The encoded protein is evolutionarily conserved and is required for the integrity and ubiquitin ligase activity of the anaphase promoting complex. Pseudogenes and splice variants have been found for this gene; however, the biological validity of some of the splice variants has not been determined. [provided by RefSeq, Nov 2008]

ANAPC13 (HGNC:):

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
ANAPC13	NM_015391.4	c.43A>T	p.Ile15Phe	missense_variant	2/3	ENST00000354910.10	NP_056206.1
ANAPC13	NM_001242374.1	c.43A>T	p.Ile15Phe	missense_variant	2/3		NP_001229303.1
ANAPC13	NM_001242375.1	c.43A>T	p.Ile15Phe	missense_variant	2/3		NP_001229304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC13	ENST00000354910.10	c.43A>T	p.Ile15Phe	missense_variant	2/3	1	NM_015391.4	ENSP00000346987.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Aug 20, 2024

The c.43A>T (p.I15F) alteration is located in exon 2 (coding exon 1) of the ANAPC13 gene. This alteration results from a A to T substitution at nucleotide position 43, causing the isoleucine (I) at amino acid position 15 to be replaced by a phenylalanine (F). 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	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	.;.;.;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.54	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.77	P;P;P;P
Vest4		0.75
MutPred		0.65		Loss of stability (P = 0.0404);Loss of stability (P = 0.0404);Loss of stability (P = 0.0404);Loss of stability (P = 0.0404);
MVP		0.43
MPC		0.23
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-134201704;