Variant 2-111778685-G-T 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.5375C>A(p.Ala1792Glu) variant causes a missense change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 14)

Exomes 𝑓: 0.000014 ( 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: 9.28

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 1 ACMG points.

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.5375C>A	p.Ala1792Glu	missense_variant	45/48	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.5375C>A	p.Ala1792Glu	missense_variant	45/48	1	NM_022662.4	ENSP00000339109.3	Q9H1A4
ANAPC1	ENST00000427997.5 linkuse as main transcript	c.3977C>A	p.Ala1326Glu	missense_variant	34/37	1		ENSP00000396695.1	H0Y564
ANAPC1	ENST00000462785.1 linkuse as main transcript	n.2069C>A		non_coding_transcript_exon_variant	1/4	2
ANAPC1	ENST00000643447.1 linkuse as main transcript	n.401C>A		non_coding_transcript_exon_variant	5/12			ENSP00000494863.1	A0A2R8YF63

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

117670

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

AC:

AN:

202458

Hom.:

AF XY:

0.00000908

AC XY:

AN XY:

110086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000131

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000136

AC:

AN:

1326742

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

666530

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.0000735

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

117670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55352

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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

ExAC

AF:

0.00000826

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 30, 2024

The c.5375C>A (p.A1792E) alteration is located in exon 45 (coding exon 44) of the ANAPC1 gene. This alteration results from a C to A substitution at nucleotide position 5375, causing the alanine (A) at amino acid position 1792 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

0.61

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.18

REVEL

Uncertain

0.37

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.61

Vest4

0.96

MutPred

0.48

Loss of MoRF binding (P = 0.0777);

MVP

0.27

ClinPred

0.91

GERP RS

4.0

Varity_R

0.35

gMVP

0.72

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