12-110381954-GAAAAAAAAA-GAAAAAAA

Variant names:

• chr12-110381954-GAA-G
• rs35699984
• NM_016238.3:c.936-8_936-7delTT

Variant summary

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

The NM_016238.3(ANAPC7):​c.936-8_936-7delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 958,654 control chromosomes in the GnomAD database, including 569 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (362 hom., cov: 0)
  • Exomes 𝑓: 0.081 (207 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: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 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.936-8_936-7delTT		splice_region intron	N/A	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.978-8_978-7delTT		splice_region intron	N/A	NP_001372137.1
	ANAPC7	NM_001137664.2		c.936-8_936-7delTT		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.936-8_936-7delTT		splice_region intron	N/A	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.936-8_936-7delTT		splice_region intron	N/A	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000471602.6	TSL:1	n.424-8_424-7delTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 12233 AN: 107498 Hom.: 363 Cov.: 0

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.138

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0813 AC: 69170 AN: 851182 Hom.: 207 AF XY: 0.0812 AC XY: 34193 AN XY: 421230

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

African (AFR) AF: 0.117 AC: 2014 AN: 17150

American (AMR) AF: 0.0690 AC: 1109 AN: 16082

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 1444 AN: 12674

East Asian (EAS) AF: 0.0438 AC: 936 AN: 21384

South Asian (SAS) AF: 0.0649 AC: 2929 AN: 45156

European-Finnish (FIN) AF: 0.0781 AC: 1901 AN: 24332

Middle Eastern (MID) AF: 0.105 AC: 240 AN: 2278

European-Non Finnish (NFE) AF: 0.0820 AC: 55511 AN: 677248

Other (OTH) AF: 0.0885 AC: 3086 AN: 34878

⚠️ 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 AF: 0.114 AC: 12227 AN: 107472 Hom.: 362 Cov.: 0 AF XY: 0.112 AC XY: 5687 AN XY: 50712

African (AFR) AF: 0.166 AC: 4783 AN: 28838

American (AMR) AF: 0.0750 AC: 759 AN: 10118

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 450 AN: 2624

East Asian (EAS) AF: 0.0243 AC: 77 AN: 3168

South Asian (SAS) AF: 0.121 AC: 353 AN: 2912

European-Finnish (FIN) AF: 0.0575 AC: 283 AN: 4922

Middle Eastern (MID) AF: 0.142 AC: 27 AN: 190

European-Non Finnish (NFE) AF: 0.0996 AC: 5232 AN: 52556

Other (OTH) AF: 0.120 AC: 171 AN: 1422

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;