12-110377558-T-C

Variant names:

• chr12-110377558-T-C
• NM_016238.3:c.1192A>G

Variant summary

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

The NM_016238.3(ANAPC7):​c.1192A>G​(p.Asn398Asp) 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: ANAPC7 NM_016238.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

Genes affected

ANAPC7 (HGNC:17380): (anaphase promoting complex subunit 7) This gene encodes a tetratricopeptide repeat containing component of the anaphase promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for proper protein ubiquitination function of APC/C and for the interaction of APC/C with certain transcription coactivators. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

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 rank	MANE	Protein	UniProt
ANAPC7	NM_016238.3	c.1192A>G	p.Asn398Asp	missense_variant	Exon 9 of 11	ENST00000455511.9	NP_057322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC7	ENST00000455511.9	c.1192A>G	p.Asn398Asp	missense_variant	Exon 9 of 11	1	NM_016238.3	ENSP00000394394.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1294A>G (p.N432D) alteration is located in exon 9 (coding exon 9) of the ANAPC7 gene. This alteration results from a A to G substitution at nucleotide position 1294, causing the asparagine (N) at amino acid position 432 to be replaced by an aspartic acid (D). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	0.065	D
MutationAssessor	Benign	1.5	L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.23
Sift	Benign	0.12	T;T
Sift4G	Benign	0.29	T;D
Polyphen		0.70	P;D
Vest4		0.70
MutPred		0.50		Gain of phosphorylation at Y434 (P = 0.0969);Gain of phosphorylation at Y434 (P = 0.0969);
MVP		0.76
MPC		1.3
ClinPred		0.77	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.57

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: chr12-110815363;