Variant chr2-111772473-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_022662.4(ANAPC1):c.5587G>A(p.Gly1863Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000297 in 1,414,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ANAPC1
NM_022662.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Variant links:

Genes affected

ANAPC1 (HGNC:19988): (anaphase promoting complex subunit 1) This gene encodes a subunit of the anaphase-promoting complex. This complex is an E3 ubiquitin ligase that regulates progression through the metaphase to anaphase portion of the cell cycle by ubiquitinating proteins which targets them for degradation. [provided by RefSeq, Dec 2011]

ANAPC1 links:

ANAPC1 (HGNC:):

ANAPC1 links:

Genome browser will be placed here

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;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ANAPC1. . Gene score misZ 0.98694 (greater than the threshold 3.09). Trascript score misZ 5.2521 (greater than threshold 3.09). GenCC has associacion of gene with Rothmund-Thomson syndrome type 1.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC1	NM_022662.4 linkuse as main transcript	c.5587G>A	p.Gly1863Arg	missense_variant, splice_region_variant	47/48	ENST00000341068.8	NP_073153.1	Q9H1A4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANAPC1	ENST00000341068.8 linkuse as main transcript	c.5587G>A	p.Gly1863Arg	missense_variant, splice_region_variant	47/48	1	NM_022662.4	ENSP00000339109.3	Q9H1A4
ANAPC1	ENST00000427997.5 linkuse as main transcript	c.4189G>A	p.Gly1397Arg	missense_variant, splice_region_variant	36/37	1		ENSP00000396695.1	H0Y564
ANAPC1	ENST00000462785.1 linkuse as main transcript	n.2281G>A		splice_region_variant, non_coding_transcript_exon_variant	3/4	2
ANAPC1	ENST00000643447.1 linkuse as main transcript	n.613G>A		splice_region_variant, non_coding_transcript_exon_variant	7/12			ENSP00000494863.1	A0A2R8YF63

Frequencies

GnomAD3 genomes

AF:

0.000173

AC:

AN:

144800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000622

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000697

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000380

AC:

AN:

131686

Hom.:

AF XY:

0.0000283

AC XY:

AN XY:

70664

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000170

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1269312

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

629492

show subpopulations

Gnomad4 AFR exome

AF:

0.000311

Gnomad4 AMR exome

AF:

0.0000294

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000545

Gnomad4 SAS exome

AF:

0.0000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000311

Gnomad4 OTH exome

AF:

0.0000188

GnomAD4 genome

AF:

0.000173

AC:

AN:

144918

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

70324

show subpopulations

Gnomad4 AFR

AF:

0.000620

Gnomad4 AMR

AF:

0.0000696

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000204

ExAC

AF:

0.0000251

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

Jul 08, 2022

The c.5587G>A (p.G1863R) alteration is located in exon 47 (coding exon 46) of the ANAPC1 gene. This alteration results from a G to A substitution at nucleotide position 5587, causing the glycine (G) at amino acid position 1863 to be replaced by an arginine (R). 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

Benign

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Benign

0.034

Sift4G

Benign

0.47

Polyphen

0.97

Vest4

0.74

MutPred

0.39

Gain of helix (P = 0.0696);

MVP

0.46

ClinPred

0.12

GERP RS

4.3

Varity_R

0.088

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.33

Position offset: -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