Genetic Variant ANAPC7:c.936-11_936-7delTTTTT (chr12-110381954-GAAAAA-G) – 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.936-11_936-7delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000584 in 975,198 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00066 ( 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:

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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.936-11_936-7delTTTTT	splice_region intron	N/A	NP_057322.3	Q9UJX3-1
ANAPC7	NM_001385208.1		c.978-11_978-7delTTTTT	splice_region intron	N/A	NP_001372137.1
ANAPC7	NM_001137664.2		c.936-11_936-7delTTTTT	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.936-11_936-7delTTTTT	splice_region intron	N/A	ENSP00000394394.4	Q9UJX3-1
ANAPC7	ENST00000450008.3	TSL:1	c.936-11_936-7delTTTTT	splice_region intron	N/A	ENSP00000402314.3	Q9UJX3-2
ANAPC7	ENST00000471602.6	TSL:1	n.424-11_424-7delTTTTT	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000928

AC:

AN:

107704

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000656

AC:

569

AN:

867494

Hom.:

AF XY:

0.000701

AC XY:

301

AN XY:

429414

show subpopulations

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

African (AFR)

AF:

0.000631

AC:

AN:

17444

American (AMR)

AF:

0.000965

AC:

AN:

16580

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

12990

East Asian (EAS)

AF:

0.00115

AC:

AN:

21686

South Asian (SAS)

AF:

0.000474

AC:

AN:

46394

European-Finnish (FIN)

AF:

0.000878

AC:

AN:

25054

Middle Eastern (MID)

AF:

0.000435

AC:

AN:

2300

European-Non Finnish (NFE)

AF:

0.000627

AC:

432

AN:

689462

Other (OTH)

AF:

0.000703

AC:

AN:

35584

⚠️ 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: 0.272

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00000928

AC:

AN:

107704

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

50812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28816

American (AMR)

AF:

0.00

AC:

AN:

10126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2626

East Asian (EAS)

AF:

0.00

AC:

AN:

3188

South Asian (SAS)

AF:

0.00

AC:

AN:

2944

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

52700

Other (OTH)

AF:

0.00

AC:

AN:

1430

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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12-110381954-GAAAAAAAAA-GAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over