12-110381954-GAAAAAAA-GAAA

Variant names:

• chr12-110381954-GAAAA-G
• rs35699984
• NM_016238.3:c.936-10_936-7delTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016238.3(ANAPC7):​c.936-10_936-7delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 973,458 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0017 (0 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000743 AC: 8 AN: 107704 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00173 AC: 1499 AN: 865754 Hom.: 0 AF XY: 0.00172 AC XY: 737 AN XY: 428504

Gnomad4 AFR exome AF: 0.00218

Gnomad4 AMR exome AF: 0.00261

Gnomad4 ASJ exome AF: 0.00200

Gnomad4 EAS exome AF: 0.00213

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.00252

Gnomad4 NFE exome AF: 0.00168

Gnomad4 OTH exome AF: 0.00197

GnomAD4 genome AF: 0.0000743 AC: 8 AN: 107704 Hom.: 0 Cov.: 0 AF XY: 0.0000590 AC XY: 3 AN XY: 50812

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000203

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.00

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;