chr12-110388538-CA-C

Variant names:

• chr12-110388538-CA-C
• NM_016238.3:c.493delT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016238.3(ANAPC7):​c.493delT​(p.Cys165AlafsTer3) variant causes a frameshift 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 (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANAPC7 NM_016238.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• Publications: 0 publications found

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]

ANAPC7 Gene-Disease associations (from GenCC):

• Ferguson-Bonni neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000258210 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016238.3. 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
	ANAPC7	NM_016238.3	MANE Select	c.493delT	p.Cys165AlafsTer3	frameshift	Exon 4 of 11	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.535delT	p.Cys179AlafsTer3	frameshift	Exon 4 of 11	NP_001372137.1
	ANAPC7	NM_001137664.2		c.493delT	p.Cys165AlafsTer3	frameshift	Exon 4 of 10	NP_001131136.2	Q9UJX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC7	ENST00000455511.9	TSL:1 MANE Select	c.493delT	p.Cys165AlafsTer3	frameshift	Exon 4 of 11	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.493delT	p.Cys165AlafsTer3	frameshift	Exon 4 of 10	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000880053.1		c.595delT	p.Cys199AlafsTer3	frameshift	Exon 5 of 12	ENSP00000550112.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Ferguson-Bonni neurodevelopmental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: -26

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr12-110826343;