chr12-110381954-G-GAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016238.3(ANAPC7):​c.936-8_936-7dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.011 (6 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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_936-7dupTT		splice_region intron	N/A	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.978-8_978-7dupTT		splice_region intron	N/A	NP_001372137.1
	ANAPC7	NM_001137664.2		c.936-8_936-7dupTT		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_936-6insTT		splice_region intron	N/A	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.936-7_936-6insTT		splice_region intron	N/A	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000471602.6	TSL:1	n.424-7_424-6insTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000130 AC: 14 AN: 107682 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000190

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0110 AC: 9515 AN: 865892 Hom.: 6 Cov.: 0 AF XY: 0.0119 AC XY: 5089 AN XY: 428348

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

African (AFR) AF: 0.00987 AC: 172 AN: 17428

American (AMR) AF: 0.0188 AC: 310 AN: 16478

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 205 AN: 12956

East Asian (EAS) AF: 0.0158 AC: 343 AN: 21644

South Asian (SAS) AF: 0.0365 AC: 1673 AN: 45832

European-Finnish (FIN) AF: 0.0114 AC: 285 AN: 24950

Middle Eastern (MID) AF: 0.0153 AC: 35 AN: 2294

European-Non Finnish (NFE) AF: 0.00882 AC: 6077 AN: 688774

Other (OTH) AF: 0.0117 AC: 415 AN: 35536

⚠️ 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: 0.000130 AC: 14 AN: 107658 Hom.: 0 Cov.: 0 AF XY: 0.000118 AC XY: 6 AN XY: 50804

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

African (AFR) AF: 0.000139 AC: 4 AN: 28854

American (AMR) AF: 0.00 AC: 0 AN: 10120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2626

East Asian (EAS) AF: 0.00 AC: 0 AN: 3172

South Asian (SAS) AF: 0.00 AC: 0 AN: 2924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4936

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

European-Non Finnish (NFE) AF: 0.000190 AC: 10 AN: 52676

Other (OTH) AF: 0.00 AC: 0 AN: 1432

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000996805), which strongly suggests a high chance of mosaicism in these individuals.

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

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

Other links and lift over

dbSNP: rs35699984; hg19: chr12-110819759;