Variant chr8-143538865-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000262577.6(ZC3H3):c.502C>T(p.Arg168Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,612,228 control chromosomes in the GnomAD database, including 15,179 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1378 hom., cov: 34)

Exomes 𝑓: 0.13 ( 13801 hom. )

Consequence

ZC3H3
ENST00000262577.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.580

Variant links:

Genes affected

ZC3H3 (HGNC:28972): (zinc finger CCCH-type containing 3) Predicted to enable SMAD binding activity. Involved in regulation of mRNA polyadenylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZC3H3 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=8.5929036E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZC3H3	NM_015117.3 linkuse as main transcript	c.502C>T	p.Arg168Trp	missense_variant	2/12	ENST00000262577.6	NP_055932.2
ZC3H3	XM_011516943.3 linkuse as main transcript	c.502C>T	p.Arg168Trp	missense_variant	2/10		XP_011515245.2
ZC3H3	XM_011516944.3 linkuse as main transcript	c.502C>T	p.Arg168Trp	missense_variant	2/5		XP_011515246.2
ZC3H3	XR_928313.4 linkuse as main transcript	n.528C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H3	ENST00000262577.6 linkuse as main transcript	c.502C>T	p.Arg168Trp	missense_variant	2/12	1	NM_015117.3	ENSP00000262577	P1	Q8IXZ2-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18080

AN:

152184

Hom.:

1371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.138

AC:

34021

AN:

247154

Hom.:

2524

AF XY:

0.141

AC XY:

18911

AN XY:

134580

show subpopulations

Gnomad AFR exome

AF:

0.0365

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.135

AC:

196820

AN:

1459926

Hom.:

13801

Cov.:

AF XY:

0.136

AC XY:

98940

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.0365

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.119

AC:

18110

AN:

152302

Hom.:

1378

Cov.:

AF XY:

0.125

AC XY:

9337

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.129

Hom.:

2652

Bravo

AF:

0.109

TwinsUK

AF:

0.132

AC:

491

ALSPAC

AF:

0.140

AC:

538

ESP6500AA

AF:

0.0391

AC:

172

ESP6500EA

AF:

0.129

AC:

1105

ExAC

AF:

0.133

AC:

16142

Asia WGS

AF:

0.160

AC:

555

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.64

MetaRNN

Benign

0.00086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

REVEL

Benign

0.050

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.0

Vest4

0.066

ClinPred

0.015

GERP RS

2.7

Varity_R

0.044

gMVP

0.13

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