Variant 19-47066585-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015168.2(ZC3H4):c.3683C>G(p.Ala1228Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0208 in 1,595,726 control chromosomes in the GnomAD database, including 5,336 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 2718 hom., cov: 33)

Exomes 𝑓: 0.012 ( 2618 hom. )

Consequence

ZC3H4
NM_015168.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.43

Variant links:

Genes affected

ZC3H4 (HGNC:17808): (zinc finger CCCH-type containing 4) This gene encodes a member of a family of CCCH (C-x8-C-x5-C-x3-H type) zinc finger domain-containing proteins. These zinc finger domains, which coordinate zinc finger binding and are characterized by three cysteine residues and one histidine residue, are nucleic acid-binding. Other family members are known to function in post-transcriptional regulation. [provided by RefSeq, Aug 2011]

ZC3H4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005467564).

BP6

Variant 19-47066585-G-C is Benign according to our data. Variant chr19-47066585-G-C is described in ClinVar as [Benign]. Clinvar id is 3055300.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H4	NM_015168.2 linkuse as main transcript	c.3683C>G	p.Ala1228Gly	missense_variant	15/15	ENST00000253048.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZC3H4	ENST00000253048.10 linkuse as main transcript	c.3683C>G	p.Ala1228Gly	missense_variant	15/15	1	NM_015168.2	P1
ZC3H4	ENST00000601973.1 linkuse as main transcript	c.2504C>G	p.Ala835Gly	missense_variant	8/8	5
ZC3H4	ENST00000594019.5 linkuse as main transcript	n.1533C>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15890

AN:

152088

Hom.:

2698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.0837

GnomAD3 exomes

AF:

0.0281

AC:

6295

AN:

223836

Hom.:

975

AF XY:

0.0223

AC XY:

2748

AN XY:

123004

show subpopulations

Gnomad AFR exome

AF:

0.382

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00178

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0119

AC:

17181

AN:

1443520

Hom.:

2618

Cov.:

AF XY:

0.0104

AC XY:

7452

AN XY:

715778

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.0246

Gnomad4 ASJ exome

AF:

0.0259

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.0000392

Gnomad4 NFE exome

AF:

0.000813

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.105

AC:

15950

AN:

152206

Hom.:

2718

Cov.:

AF XY:

0.100

AC XY:

7460

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.0828

Alfa

AF:

0.0418

Hom.:

239

Bravo

AF:

0.122

ESP6500AA

AF:

0.289

AC:

906

ESP6500EA

AF:

0.00206

AC:

ExAC

AF:

0.0306

AC:

3579

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZC3H4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.088

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.9

REVEL

Benign

0.10

Sift

Benign

0.053

Sift4G

Benign

0.22

Polyphen

0.95

Vest4

0.052

MPC

0.11

ClinPred

0.039

GERP RS

2.4

Varity_R

0.066

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