12-110381954-GAAAAAAAAA-GAAAAAAAAAA

Variant names:

• chr12-110381954-G-GA
• rs35699984
• NM_016238.3:c.936-7dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_016238.3(ANAPC7):​c.936-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0056 (7 hom., cov: 0)
  • Exomes 𝑓: 0.051 (95 hom.)
• Consequence: ANAPC7 NM_016238.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 5 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.00564 AC: 607 AN: 107644 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00187

Gnomad AMI AF: 0.0125

Gnomad AMR AF: 0.000790

Gnomad ASJ AF: 0.00420

Gnomad EAS AF: 0.00314

Gnomad SAS AF: 0.00442

Gnomad FIN AF: 0.00365

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00908

Gnomad OTH AF: 0.00420

GnomAD4 exome AF: 0.0510 AC: 44101 AN: 864504 Hom.: 95 Cov.: 0 AF XY: 0.0534 AC XY: 22859 AN XY: 427716

African (AFR) AF: 0.0477 AC: 832 AN: 17428

American (AMR) AF: 0.0639 AC: 1053 AN: 16486

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 903 AN: 12934

East Asian (EAS) AF: 0.0975 AC: 2103 AN: 21560

South Asian (SAS) AF: 0.113 AC: 5172 AN: 45958

European-Finnish (FIN) AF: 0.0554 AC: 1382 AN: 24930

Middle Eastern (MID) AF: 0.0640 AC: 146 AN: 2282

European-Non Finnish (NFE) AF: 0.0443 AC: 30470 AN: 687498

Other (OTH) AF: 0.0576 AC: 2040 AN: 35428

GnomAD4 genome AF: 0.00565 AC: 608 AN: 107620 Hom.: 7 Cov.: 0 AF XY: 0.00492 AC XY: 250 AN XY: 50782

African (AFR) AF: 0.00187 AC: 54 AN: 28848

American (AMR) AF: 0.000791 AC: 8 AN: 10118

Ashkenazi Jewish (ASJ) AF: 0.00420 AC: 11 AN: 2622

East Asian (EAS) AF: 0.00315 AC: 10 AN: 3172

South Asian (SAS) AF: 0.00446 AC: 13 AN: 2918

European-Finnish (FIN) AF: 0.00365 AC: 18 AN: 4930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 194

European-Non Finnish (NFE) AF: 0.00910 AC: 479 AN: 52664

Other (OTH) AF: 0.00419 AC: 6 AN: 1432

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35699984; hg19: chr12-110819759;