chr12-110381954-GAAA-G

Variant names:

• chr12-110381954-GAAA-G
• rs35699984
• NM_016238.3:c.936-9_936-7delTTT

Variant summary

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

The NM_016238.3(ANAPC7):​c.936-9_936-7delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 969,706 control chromosomes in the GnomAD database, including 5 homozygotes. 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 0.0011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0071 (5 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 5 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.936-9_936-7delTTT		splice_region intron	N/A	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.978-9_978-7delTTT		splice_region intron	N/A	NP_001372137.1
	ANAPC7	NM_001137664.2		c.936-9_936-7delTTT		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.936-9_936-7delTTT		splice_region intron	N/A	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.936-9_936-7delTTT		splice_region intron	N/A	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000471602.6	TSL:1	n.424-9_424-7delTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 115 AN: 107698 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00378

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000340

Gnomad FIN AF: 0.000203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000759

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00705 AC: 6078 AN: 862032 Hom.: 5 AF XY: 0.00703 AC XY: 3000 AN XY: 426584

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

African (AFR) AF: 0.0129 AC: 224 AN: 17324

American (AMR) AF: 0.00893 AC: 146 AN: 16356

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 130 AN: 12854

East Asian (EAS) AF: 0.00547 AC: 118 AN: 21570

South Asian (SAS) AF: 0.00429 AC: 198 AN: 46126

European-Finnish (FIN) AF: 0.00956 AC: 237 AN: 24782

Middle Eastern (MID) AF: 0.0105 AC: 24 AN: 2288

European-Non Finnish (NFE) AF: 0.00685 AC: 4695 AN: 685384

Other (OTH) AF: 0.00866 AC: 306 AN: 35348

⚠️ 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: 0.00107 AC: 115 AN: 107674 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 55 AN XY: 50814

African (AFR) AF: 0.00378 AC: 109 AN: 28856

American (AMR) AF: 0.00 AC: 0 AN: 10122

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3170

South Asian (SAS) AF: 0.000342 AC: 1 AN: 2924

European-Finnish (FIN) AF: 0.000203 AC: 1 AN: 4936

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

European-Non Finnish (NFE) AF: 0.0000759 AC: 4 AN: 52690

Other (OTH) AF: 0.00 AC: 0 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;