rs192085565

Variant names:

• chr12-110378547-C-A
• rs192085565
• NM_016238.3:c.1133-930G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-110378547-C-A
• chr12-110378547-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016238.3(ANAPC7):​c.1133-930G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 152,318 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANAPC7 NM_016238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.1133-930G>T		intron	N/A	NP_057322.3	Q9UJX3-1
	ANAPC7	NM_001385208.1		c.1175-930G>T		intron	N/A	NP_001372137.1
	ANAPC7	NM_001137664.2		c.1133-930G>T		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.1133-930G>T		intron	N/A	ENSP00000394394.4	Q9UJX3-1
	ANAPC7	ENST00000450008.3	TSL:1	c.1133-930G>T		intron	N/A	ENSP00000402314.3	Q9UJX3-2
	ANAPC7	ENST00000471602.6	TSL:1	n.621-930G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 703 AN: 152200 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00600

Gnomad OTH AF: 0.00669

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 70 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 60

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.00462 AC: 703 AN: 152318 Hom.: 1 Cov.: 32 AF XY: 0.00419 AC XY: 312 AN XY: 74476

African (AFR) AF: 0.000986 AC: 41 AN: 41580

American (AMR) AF: 0.0111 AC: 169 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00600 AC: 408 AN: 68032

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00133 Hom.: 0

Bravo AF: 0.00539

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.50
PhyloP100		-0.40

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: rs192085565; hg19: chr12-110816352;