Variant 7-130023656-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016478.5(ZC3HC1):c.1088G>A(p.Arg363His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,613,734 control chromosomes in the GnomAD database, including 100,561 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 6492 hom., cov: 32)

Exomes 𝑓: 0.35 ( 94069 hom. )

Consequence

ZC3HC1
NM_016478.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

ZC3HC1 (HGNC:29913): (zinc finger C3HC-type containing 1) This gene encodes an F-box-containing protein that is a component of an SCF-type E3 ubiquitin ligase complex that regulates the onset of cell division. The G2/M transition in the cell cycle requires the interaction of the proteins cyclin B1 and cyclin-dependent kinase 1. The activated ubiquitin ligase complex targets the protein cyclin B1 for degradation, preventing this transition to mitosis. [provided by RefSeq, Aug 2013]

ZC3HC1 links:

ZC3HC1 (HGNC:):

ZC3HC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018992424).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3HC1	NM_016478.5 linkuse as main transcript	c.1088G>A	p.Arg363His	missense_variant	8/10	ENST00000358303.9	NP_057562.3	Q86WB0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZC3HC1	ENST00000358303.9 linkuse as main transcript	c.1088G>A	p.Arg363His	missense_variant	8/10	1	NM_016478.5	ENSP00000351052.4	Q86WB0-1
ZC3HC1	ENST00000481503.5 linkuse as main transcript	c.959G>A	p.Arg320His	missense_variant	8/10	5		ENSP00000418533.1	C9J0I9
ZC3HC1	ENST00000467642.5 linkuse as main transcript	n.*972G>A		non_coding_transcript_exon_variant	9/11	2		ENSP00000419509.1	F8WF13
ZC3HC1	ENST00000648450.1 linkuse as main transcript	n.*1098G>A		non_coding_transcript_exon_variant	10/12			ENSP00000498166.1	F8WAU5
ZC3HC1	ENST00000467642.5 linkuse as main transcript	n.*972G>A		3_prime_UTR_variant	9/11	2		ENSP00000419509.1	F8WF13
ZC3HC1	ENST00000648450.1 linkuse as main transcript	n.*1098G>A		3_prime_UTR_variant	10/12			ENSP00000498166.1	F8WAU5

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39248

AN:

151858

Hom.:

6494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.0537

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.275

AC:

69236

AN:

251378

Hom.:

11670

AF XY:

0.282

AC XY:

38258

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0669

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.395

Gnomad EAS exome

AF:

0.0572

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.376

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.346

AC:

505616

AN:

1461758

Hom.:

94069

Cov.:

AF XY:

0.343

AC XY:

249277

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0601

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.389

Gnomad4 EAS exome

AF:

0.0394

Gnomad4 SAS exome

AF:

0.198

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.258

AC:

39238

AN:

151976

Hom.:

6492

Cov.:

AF XY:

0.253

AC XY:

18780

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.0744

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.0536

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.312

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.261

Alfa

AF:

0.350

Hom.:

21676

Bravo

AF:

0.244

TwinsUK

AF:

0.396

AC:

1468

ALSPAC

AF:

0.399

AC:

1537

ESP6500AA

AF:

0.0815

AC:

359

ESP6500EA

AF:

0.383

AC:

3290

ExAC

AF:

0.273

AC:

33132

Asia WGS

AF:

0.134

AC:

465

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.369

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

T;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0050

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.36

MPC

0.91

ClinPred

0.019

GERP RS

5.5

Varity_R

0.18

gMVP

0.26

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