dbSNP rs149257210: ZC3HC1:p.Ala452Pro (chr7-130022405-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016478.5(ZC3HC1):c.1354G>C(p.Ala452Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. A452T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZC3HC1
NM_016478.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.14

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058791697).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016478.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC3HC1	NM_016478.5	MANE Select	c.1354G>C	p.Ala452Pro	missense	Exon 9 of 10	NP_057562.3
ZC3HC1	NM_001282190.2		c.1291G>C	p.Ala431Pro	missense	Exon 10 of 11	NP_001269119.1	Q86WB0-2
ZC3HC1	NM_001363701.1		c.1225G>C	p.Ala409Pro	missense	Exon 9 of 10	NP_001350630.1	C9J0I9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC3HC1	ENST00000358303.9	TSL:1 MANE Select	c.1354G>C	p.Ala452Pro	missense	Exon 9 of 10	ENSP00000351052.4	Q86WB0-1
ZC3HC1	ENST00000481503.5	TSL:5	c.1225G>C	p.Ala409Pro	missense	Exon 9 of 10	ENSP00000418533.1	C9J0I9
ZC3HC1	ENST00000467642.5	TSL:2	n.*1238G>C		non_coding_transcript_exon	Exon 10 of 11	ENSP00000419509.1	F8WF13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249758

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460804

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726642

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111494

Other (OTH)

AF:

0.00

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0030

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.51

M_CAP

Benign

0.0086

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-4.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.0

REVEL

Benign

0.022

Sift

Benign

0.14

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.10

MutPred

0.26

Gain of catalytic residue at A452 (P = 0.0119)

MVP

0.31

MPC

0.31

ClinPred

0.070

GERP RS

-9.6

Varity_R

0.057

gMVP

0.066

Mutation Taster

=91/9

polymorphism

(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