NM_016478.5:c.1088G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R363C) has been classified as Uncertain significance.

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

Publications

232 publications found

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:

UBE2H-DT (HGNC:55615): (UBE2H divergent transcript)

UBE2H-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZC3HC1	NM_016478.5 link	c.1088G>A	p.Arg363His	missense_variant	Exon 8 of 10	ENST00000358303.9	NP_057562.3	Q86WB0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZC3HC1	ENST00000358303.9 link	c.1088G>A	p.Arg363His	missense_variant	Exon 8 of 10	1	NM_016478.5	ENSP00000351052.4	Q86WB0-1
ZC3HC1	ENST00000481503.5 link	c.959G>A	p.Arg320His	missense_variant	Exon 8 of 10	5		ENSP00000418533.1	C9J0I9
ZC3HC1	ENST00000467642.5 link	n.*972G>A		non_coding_transcript_exon_variant	Exon 9 of 11	2		ENSP00000419509.1	F8WF13
ZC3HC1	ENST00000470651.2 link	n.*1041G>A		non_coding_transcript_exon_variant	Exon 9 of 11	4		ENSP00000420068.1	F8WDK5
ZC3HC1	ENST00000484432.2 link	n.*902G>A		non_coding_transcript_exon_variant	Exon 8 of 10	4		ENSP00000417217.1	F8WAU5
ZC3HC1	ENST00000648450.1 link	n.*1098G>A		non_coding_transcript_exon_variant	Exon 10 of 12			ENSP00000498166.1	F8WAU5
ZC3HC1	ENST00000467642.5 link	n.*972G>A		3_prime_UTR_variant	Exon 9 of 11	2		ENSP00000419509.1	F8WF13
ZC3HC1	ENST00000470651.2 link	n.*1041G>A		3_prime_UTR_variant	Exon 9 of 11	4		ENSP00000420068.1	F8WDK5
ZC3HC1	ENST00000484432.2 link	n.*902G>A		3_prime_UTR_variant	Exon 8 of 10	4		ENSP00000417217.1	F8WAU5
ZC3HC1	ENST00000648450.1 link	n.*1098G>A		3_prime_UTR_variant	Exon 10 of 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

GnomAD2 exomes

AF:

0.275

AC:

69236

AN:

251378

AF XY:

0.282

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 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

African (AFR)

AF:

0.0601

AC:

2011

AN:

33480

American (AMR)

AF:

0.170

AC:

7608

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

10160

AN:

26134

East Asian (EAS)

AF:

0.0394

AC:

1565

AN:

39700

South Asian (SAS)

AF:

0.198

AC:

17034

AN:

86242

European-Finnish (FIN)

AF:

0.321

AC:

17153

AN:

53418

Middle Eastern (MID)

AF:

0.248

AC:

1430

AN:

5768

European-Non Finnish (NFE)

AF:

0.386

AC:

429214

AN:

1111900

Other (OTH)

AF:

0.322

AC:

19441

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17744

35488

53232

70976

88720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13070

26140

39210

52280

65350

<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:

0.258

AC:

39238

AN:

151976

Hom.:

6492

Cov.:

AF XY:

0.253

AC XY:

18780

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0744

AC:

3085

AN:

41478

American (AMR)

AF:

0.223

AC:

3400

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1321

AN:

3470

East Asian (EAS)

AF:

0.0536

AC:

278

AN:

5184

South Asian (SAS)

AF:

0.183

AC:

882

AN:

4814

European-Finnish (FIN)

AF:

0.312

AC:

3277

AN:

10514

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26002

AN:

67948

Other (OTH)

AF:

0.261

AC:

549

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1358

2715

4073

5430

6788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.335

Hom.:

40208

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

(source)

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;.;.

PhyloP100

2.0

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

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over