chr12-110381953-AG-AGA

Variant names:

• chr12-110381952-GAG-GA
• rs553248526
• NM_016238.3:c.936-6delC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016238.3(ANAPC7):​c.936-6delC 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 0.0011 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANAPC7 NM_016238.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 76 AN: 69890 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00472

Gnomad AMR AF: 0.00104

Gnomad ASJ AF: 0.000535

Gnomad EAS AF: 0.00191

Gnomad SAS AF: 0.000412

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000901

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00226 AC: 96 AN: 42418 AF XY: 0.00234

Gnomad AFR exome AF: 0.00440

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.000842

Gnomad EAS exome AF: 0.00885

Gnomad FIN exome AF: 0.000880

Gnomad NFE exome AF: 0.00125

Gnomad OTH exome AF: 0.00315

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00310 AC: 1635 AN: 528022 Hom.: 0 Cov.: 15 AF XY: 0.00319 AC XY: 872 AN XY: 273342

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

African (AFR) AF: 0.00479 AC: 47 AN: 9820

American (AMR) AF: 0.00333 AC: 54 AN: 16214

Ashkenazi Jewish (ASJ) AF: 0.00334 AC: 35 AN: 10466

East Asian (EAS) AF: 0.00853 AC: 136 AN: 15942

South Asian (SAS) AF: 0.00375 AC: 181 AN: 48284

European-Finnish (FIN) AF: 0.00319 AC: 68 AN: 21308

Middle Eastern (MID) AF: 0.00663 AC: 11 AN: 1658

European-Non Finnish (NFE) AF: 0.00271 AC: 1036 AN: 381970

Other (OTH) AF: 0.00300 AC: 67 AN: 22360

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00109 AC: 76 AN: 69926 Hom.: 0 Cov.: 17 AF XY: 0.00100 AC XY: 34 AN XY: 33928

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

African (AFR) AF: 0.00186 AC: 29 AN: 15592

American (AMR) AF: 0.00103 AC: 8 AN: 7748

Ashkenazi Jewish (ASJ) AF: 0.000535 AC: 1 AN: 1870

East Asian (EAS) AF: 0.00191 AC: 4 AN: 2096

South Asian (SAS) AF: 0.000412 AC: 1 AN: 2428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 186

European-Non Finnish (NFE) AF: 0.000901 AC: 31 AN: 34420

Other (OTH) AF: 0.00 AC: 0 AN: 950

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), 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		1.3
Mutation Taster		=90/10	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs553248526; hg19: chr12-110819757;