12-110381954-GAAAAAAAAA-GAAAAAA

Variant names:

• chr12-110381954-GAAA-G
• rs35699984
• NM_016238.3:c.936-9_936-7delTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016238.3(ANAPC7):​c.936-9_936-7delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 969,706 control chromosomes in the GnomAD database, including 5 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 0.0011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0071 (5 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 115 AN: 107698 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00378

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000340

Gnomad FIN AF: 0.000203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000759

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00705 AC: 6078 AN: 862032 Hom.: 5 AF XY: 0.00703 AC XY: 3000 AN XY: 426584

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.00893

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.00547

Gnomad4 SAS exome AF: 0.00429

Gnomad4 FIN exome AF: 0.00956

Gnomad4 NFE exome AF: 0.00685

Gnomad4 OTH exome AF: 0.00866

GnomAD4 genome AF: 0.00107 AC: 115 AN: 107674 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 55 AN XY: 50814

Gnomad4 AFR AF: 0.00378

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000342

Gnomad4 FIN AF: 0.000203

Gnomad4 NFE AF: 0.0000759

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;