chr7-130023513-A-C

Position:

chr7-130023513-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016478.5(ZC3HC1):c.1231T>G(p.Ser411Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000031 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZC3HC1
NM_016478.5 missense, splice_region

Scores

Splicing: ADA: 0.007693

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13471761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3HC1	NM_016478.5 linkuse as main transcript	c.1231T>G	p.Ser411Ala	missense_variant, splice_region_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.1231T>G	p.Ser411Ala	missense_variant, splice_region_variant	8/10	1	NM_016478.5	ENSP00000351052.4	Q86WB0-1
ZC3HC1	ENST00000481503.5 linkuse as main transcript	c.1102T>G	p.Ser368Ala	missense_variant, splice_region_variant	8/10	5		ENSP00000418533.1	C9J0I9
ZC3HC1	ENST00000467642.5 linkuse as main transcript	n.*1115T>G		splice_region_variant, non_coding_transcript_exon_variant	9/11	2		ENSP00000419509.1	F8WF13
ZC3HC1	ENST00000648450.1 linkuse as main transcript	n.*1241T>G		splice_region_variant, non_coding_transcript_exon_variant	10/12			ENSP00000498166.1	F8WAU5
ZC3HC1	ENST00000467642.5 linkuse as main transcript	n.*1115T>G		3_prime_UTR_variant	9/11	2		ENSP00000419509.1	F8WF13
ZC3HC1	ENST00000648450.1 linkuse as main transcript	n.*1241T>G		3_prime_UTR_variant	10/12			ENSP00000498166.1	F8WAU5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

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

Mar 07, 2024

The c.1231T>G (p.S411A) alteration is located in exon 8 (coding exon 8) of the ZC3HC1 gene. This alteration results from a T to G substitution at nucleotide position 1231, causing the serine (S) at amino acid position 411 to be replaced by an alanine (A). 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

Benign

0.072

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.0074

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.067

T;T;T

Sift4G

Benign

0.087

T;T;T

Polyphen

0.10

B;.;B

Vest4

0.25

MutPred

0.18

Loss of phosphorylation at S411 (P = 0.0024);.;.;

MVP

0.53

MPC

0.29

ClinPred

0.65

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.086

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0077

dbscSNV1_RF

Benign

0.066

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