Genetic Variant NM_022662.4:c.5182T>C (chr2-111782389-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022662.4(ANAPC1):c.5182T>C(p.Ser1728Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANAPC1
NM_022662.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Publications

0 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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22237217).

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.5182T>C	p.Ser1728Pro	missense	Exon 43 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.5182T>C	p.Ser1728Pro	missense	Exon 43 of 48	ENSP00000339109.3	Q9H1A4
ANAPC1	ENST00000427997.5	TSL:1	c.3784T>C	p.Ser1262Pro	missense	Exon 32 of 37	ENSP00000396695.1	H0Y564
ANAPC1	ENST00000917121.1		c.5182T>C	p.Ser1728Pro	missense	Exon 43 of 48	ENSP00000587180.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000418

AC:

AN:

239282

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.0000224

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111546

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.10

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Benign

0.012

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

2.7

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.12

Sift

Benign

0.19

Sift4G

Benign

0.23

Polyphen

0.61

Vest4

0.38

MutPred

0.32

Loss of phosphorylation at S1728 (P = 0.0379)

MVP

0.26

ClinPred

0.69

GERP RS

4.2

Varity_R

0.78

gMVP

0.47

Mutation Taster

=48/52

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over