Variant chr2-111792437-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2

The NM_022662.4(ANAPC1):c.4637C>T(p.Thr1546Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 151,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANAPC1
NM_022662.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP2

Missense variant where missense usually causes diseases, ANAPC1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANAPC1	NM_022662.4 linkuse as main transcript	c.4637C>T	p.Thr1546Met	missense_variant	38/48	ENST00000341068.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ANAPC1	ENST00000341068.8 linkuse as main transcript	c.4637C>T	p.Thr1546Met	missense_variant	38/48	1	NM_022662.4	P1
ANAPC1	ENST00000427997.5 linkuse as main transcript	c.3242C>T	p.Thr1081Met	missense_variant	27/37	1
ANAPC1	ENST00000464695.1 linkuse as main transcript	n.487C>T		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000595

AC:

AN:

151260

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:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000665

AC:

AN:

240490

Hom.:

AF XY:

0.0000688

AC XY:

AN XY:

130862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0000672

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000834

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000120

AC:

175

AN:

1460952

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000595

AC:

AN:

151260

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73782

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000661

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0095

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.050

REVEL

Uncertain

0.33

Sift

Benign

0.041

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.78

MVP

0.30

ClinPred

0.29

GERP RS

4.4

Varity_R

0.11

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over