Genetic Variant ANAPC7:c.936-13_936-7dupTTTTTTT (chr12-110381954-G-GAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_016238.3(ANAPC7):c.936-13_936-7dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ANAPC7
NM_016238.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

5 publications found

Variant links:

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)

ANAPC7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANAPC7	NM_016238.3	MANE Select	c.936-13_936-7dupTTTTTTT	splice_region intron	N/A	NP_057322.3	Q9UJX3-1
ANAPC7	NM_001385208.1		c.978-13_978-7dupTTTTTTT	splice_region intron	N/A	NP_001372137.1
ANAPC7	NM_001137664.2		c.936-13_936-7dupTTTTTTT	splice_region intron	N/A	NP_001131136.2	Q9UJX3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANAPC7	ENST00000455511.9	TSL:1 MANE Select	c.936-7_936-6insTTTTTTT	splice_region intron	N/A	ENSP00000394394.4	Q9UJX3-1
ANAPC7	ENST00000450008.3	TSL:1	c.936-7_936-6insTTTTTTT	splice_region intron	N/A	ENSP00000402314.3	Q9UJX3-2
ANAPC7	ENST00000471602.6	TSL:1	n.424-7_424-6insTTTTTTT	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000186

AC:

AN:

107702

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000380

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000224

AC:

195

AN:

869278

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

116

AN XY:

430248

show subpopulations

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

African (AFR)

AF:

0.000343

AC:

AN:

17492

American (AMR)

AF:

0.000481

AC:

AN:

16626

Ashkenazi Jewish (ASJ)

AF:

0.000307

AC:

AN:

13014

East Asian (EAS)

AF:

0.000874

AC:

AN:

21750

South Asian (SAS)

AF:

0.00110

AC:

AN:

46394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25098

Middle Eastern (MID)

AF:

0.000433

AC:

AN:

2310

European-Non Finnish (NFE)

AF:

0.000149

AC:

103

AN:

690926

Other (OTH)

AF:

0.0000841

AC:

AN:

35668

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.383

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000186

AC:

AN:

107678

Hom.:

Cov.:

AF XY:

0.0000394

AC XY:

AN XY:

50816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28856

American (AMR)

AF:

0.00

AC:

AN:

10122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2626

East Asian (EAS)

AF:

0.00

AC:

AN:

3172

South Asian (SAS)

AF:

0.00

AC:

AN:

2924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.0000380

AC:

AN:

52692

Other (OTH)

AF:

0.00

AC:

AN:

1432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-110381954-GAAAAAAAAA-GAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over