12-110381954-GAAAAAAAAA-GA

Variant names:

• chr12-110381954-GAAAAAAAA-G
• rs35699984
• NM_016238.3:c.936-14_936-7delTTTTTTTT

Variant summary

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

The NM_016238.3(ANAPC7):​c.936-14_936-7delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 869,402 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: ANAPC7 NM_016238.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• 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)

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.936-14_936-7delTTTTTTTT		splice_region intron	N/A	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.978-14_978-7delTTTTTTTT		splice_region intron	N/A	NP_001372137.1
	ANAPC7	NM_001137664.2		c.936-14_936-7delTTTTTTTT		splice_region intron	N/A	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.936-14_936-7delTTTTTTTT		splice_region intron	N/A	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.936-14_936-7delTTTTTTTT		splice_region intron	N/A	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000471602.6	TSL:1	n.424-14_424-7delTTTTTTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000690 AC: 6 AN: 869402 Hom.: 0 AF XY: 0.00000697 AC XY: 3 AN XY: 430336

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17494

American (AMR) AF: 0.00 AC: 0 AN: 16632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13020

East Asian (EAS) AF: 0.0000460 AC: 1 AN: 21754

South Asian (SAS) AF: 0.00 AC: 0 AN: 46446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2310

European-Non Finnish (NFE) AF: 0.00000724 AC: 5 AN: 690970

Other (OTH) AF: 0.00 AC: 0 AN: 35674

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs35699984; hg19: chr12-110819759;