Variant 17-81894508-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000344877.10(ANAPC11):c.31G>A(p.Val11Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ANAPC11
ENST00000344877.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.36

Variant links:

Genes affected

ANAPC11 (HGNC:14452): (anaphase promoting complex subunit 11) Enables cullin family protein binding activity and ubiquitin-ubiquitin ligase activity. Contributes to ubiquitin-protein transferase activity. Involved in protein K11-linked ubiquitination. Located in nucleolus and nucleoplasm. Part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

ANAPC11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC11	NM_001002248.3 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	3/4	ENST00000344877.10	NP_001002248.1	Q9NYG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC11	ENST00000344877.10 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	3/4	1	NM_001002248.3	ENSP00000339695.5		Q9NYG5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250576

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460810

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.31G>A (p.V11M) alteration is located in exon 2 (coding exon 1) of the ANAPC11 gene. This alteration results from a G to A substitution at nucleotide position 31, causing the valine (V) at amino acid position 11 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T;T;T;.;.;T;T;T;.;.;T;T;T;.;T;T;T;.;T;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;D;.;D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.050

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.6

.;.;.;D;.;.;.;.;.;N;.;.;.;.;.;D;.;.;.;.;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.018

.;.;.;D;.;.;.;.;.;D;.;.;.;.;.;D;.;.;.;.;.

Sift4G

Uncertain

0.020

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.95

P;P;P;P;.;.;P;P;P;D;.;P;P;P;.;P;.;P;.;P;.

Vest4

0.80

MutPred

0.65

Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);Gain of MoRF binding (P = 0.0968);

MVP

0.62

MPC

1.1

ClinPred

0.99

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over