Variant 10-72224042-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173473.4(ANAPC16):c.128G>A(p.Gly43Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,602,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ANAPC16
NM_173473.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.36

Variant links:

Genes affected

ANAPC16 (HGNC:26976): (anaphase promoting complex subunit 16) Involved in protein ubiquitination. Located in cytosol and kinetochore. Part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

ANAPC16 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
ANAPC16	NM_173473.4 linkuse as main transcript	c.128G>A	p.Gly43Glu	missense_variant	2/4	ENST00000299381.5	NP_775744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC16	ENST00000299381.5 linkuse as main transcript	c.128G>A	p.Gly43Glu	missense_variant	2/4	1	NM_173473.4	ENSP00000299381	P1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000161

AC:

AN:

249210

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000971

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000103

AC:

149

AN:

1450592

Hom.:

Cov.:

AF XY:

0.0000971

AC XY:

AN XY:

720912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000678

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.0000707

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

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 07, 2022

The c.128G>A (p.G43E) alteration is located in exon 3 (coding exon 1) of the ANAPC16 gene. This alteration results from a G to A substitution at nucleotide position 128, causing the glycine (G) at amino acid position 43 to be replaced by a glutamic acid (E). 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

0.62

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;T

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

D;D;.

M_CAP

Benign

0.0036

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.55

.;N;N

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-7.0

.;.;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0060

.;.;D

Sift4G

Benign

0.22

T;T;T

Polyphen

1.0

.;D;D

Vest4

0.78

MVP

0.72

MPC

1.5

ClinPred

0.44

GERP RS

6.0

Varity_R

0.77

gMVP

0.65

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

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