12-110381954-GAAAAAAAAA-GAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016238.3(ANAPC7):​c.936-8_936-7delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 958,654 control chromosomes in the GnomAD database, including 569 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 0.11 (362 hom., cov: 0)
  • Exomes 𝑓: 0.081 (207 hom.)
• Consequence: ANAPC7 NM_016238.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANAPC7	NM_016238.3	c.936-8_936-7delTT		splice_region_variant, intron_variant	Intron 7 of 10	ENST00000455511.9	NP_057322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC7	ENST00000455511.9	c.936-8_936-7delTT		splice_region_variant, intron_variant	Intron 7 of 10	1	NM_016238.3	ENSP00000394394.4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 12233 AN: 107498 Hom.: 363 Cov.: 0

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.138

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0813 AC: 69170 AN: 851182 Hom.: 207 AF XY: 0.0812 AC XY: 34193 AN XY: 421230

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0690

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0438

Gnomad4 SAS exome AF: 0.0649

Gnomad4 FIN exome AF: 0.0781

Gnomad4 NFE exome AF: 0.0820

Gnomad4 OTH exome AF: 0.0885

GnomAD4 genome AF: 0.114 AC: 12227 AN: 107472 Hom.: 362 Cov.: 0 AF XY: 0.112 AC XY: 5687 AN XY: 50712

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0243

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0575

Gnomad4 NFE AF: 0.0996

Gnomad4 OTH AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35699984; hg19: chr12-110819759;