Genetic Variant ANAPC1:p.Gly1863Arg (chr2-111772473-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Rothmund-Thomson syndrome type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ANAPC1 links:

Genome browser will be placed here

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_022662.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC1	NM_022662.4	MANE Select	c.5587G>A	p.Gly1863Arg	missense splice_region	Exon 47 of 48	NP_073153.1	Q9H1A4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANAPC1	ENST00000341068.8	TSL:1 MANE Select	c.5587G>A	p.Gly1863Arg	missense splice_region	Exon 47 of 48	ENSP00000339109.3	Q9H1A4
ANAPC1	ENST00000427997.5	TSL:1	c.4189G>A	p.Gly1397Arg	missense splice_region	Exon 36 of 37	ENSP00000396695.1	H0Y564
ANAPC1	ENST00000917121.1		c.5629G>A	p.Gly1877Arg	missense	Exon 47 of 48	ENSP00000587180.1

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

GnomAD2 exomes

AF:

0.0000380

AC:

AN:

131686

AF XY:

0.0000283

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 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

African (AFR)

AF:

0.000311

AC:

AN:

28930

American (AMR)

AF:

0.0000294

AC:

AN:

34054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21862

East Asian (EAS)

AF:

0.0000545

AC:

AN:

36698

South Asian (SAS)

AF:

0.0000135

AC:

AN:

74288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5090

European-Non Finnish (NFE)

AF:

0.00000311

AC:

AN:

964738

Other (OTH)

AF:

0.0000188

AC:

AN:

53166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000173

AC:

AN:

144918

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

70324

show subpopulations

African (AFR)

AF:

0.000620

AC:

AN:

38722

American (AMR)

AF:

0.0000696

AC:

AN:

14374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

4762

South Asian (SAS)

AF:

0.00

AC:

AN:

4254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66324

Other (OTH)

AF:

0.00

AC:

AN:

1934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000204

ExAC

AF:

0.0000251

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

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

PhyloP100

3.9

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

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over