12-110381954-GAAAAAAAAA-GAAAAAAAA

Variant names:

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

Variant summary

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

The NM_016238.3(ANAPC7):​c.936-7delT 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 0.48 (10143 hom., cov: 0)
  • Exomes 𝑓: 0.35 (5208 hom.)
  • Failed GnomAD Quality Control
• 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 (EAS) allele frequency at 95% confidence interval = 0.51 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.936-7delT		splice_region intron	N/A	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.978-7delT		splice_region intron	N/A	NP_001372137.1
	ANAPC7	NM_001137664.2		c.936-7delT		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.936-7delT		splice_region intron	N/A	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.936-7delT		splice_region intron	N/A	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000471602.6	TSL:1	n.424-7delT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 52139 AN: 107668 Hom.: 10144 Cov.: 0

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.464

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.349 AC: 297556 AN: 853808 Hom.: 5208 Cov.: 0 AF XY: 0.342 AC XY: 144291 AN XY: 422054

African (AFR) AF: 0.324 AC: 5584 AN: 17226

American (AMR) AF: 0.277 AC: 4456 AN: 16106

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 3431 AN: 12662

East Asian (EAS) AF: 0.305 AC: 6455 AN: 21162

South Asian (SAS) AF: 0.200 AC: 8964 AN: 44754

European-Finnish (FIN) AF: 0.339 AC: 8283 AN: 24418

Middle Eastern (MID) AF: 0.274 AC: 618 AN: 2252

European-Non Finnish (NFE) AF: 0.365 AC: 248111 AN: 680208

Other (OTH) AF: 0.333 AC: 11654 AN: 35020

GnomAD4 genome AF: 0.484 AC: 52133 AN: 107644 Hom.: 10143 Cov.: 0 AF XY: 0.480 AC XY: 24394 AN XY: 50816

African (AFR) AF: 0.479 AC: 13807 AN: 28840

American (AMR) AF: 0.463 AC: 4690 AN: 10126

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1037 AN: 2618

East Asian (EAS) AF: 0.531 AC: 1689 AN: 3182

South Asian (SAS) AF: 0.364 AC: 1064 AN: 2922

European-Finnish (FIN) AF: 0.513 AC: 2530 AN: 4934

Middle Eastern (MID) AF: 0.381 AC: 74 AN: 194

European-Non Finnish (NFE) AF: 0.498 AC: 26215 AN: 52668

Other (OTH) AF: 0.464 AC: 664 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 (auto)

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; COSMIC: COSV107531142; COSMIC: COSV107531142;