dbSNP rs4873802: ZC3H3:p.Ala228Ser (chr8-143538685-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015117.3(ZC3H3):c.682G>T(p.Ala228Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,607,642 control chromosomes in the GnomAD database, including 30,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2192 hom., cov: 34)

Exomes 𝑓: 0.19 ( 27905 hom. )

Consequence

ZC3H3
NM_015117.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.289

Publications

35 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003994137).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H3	NM_015117.3 link	c.682G>T	p.Ala228Ser	missense_variant	Exon 2 of 12	ENST00000262577.6	NP_055932.2	Q8IXZ2-1
ZC3H3	XM_011516943.3 link	c.682G>T	p.Ala228Ser	missense_variant	Exon 2 of 10		XP_011515245.2
ZC3H3	XM_011516944.3 link	c.682G>T	p.Ala228Ser	missense_variant	Exon 2 of 5		XP_011515246.2
ZC3H3	XR_928313.4 link	n.708G>T		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H3	ENST00000262577.6 link	c.682G>T	p.Ala228Ser	missense_variant	Exon 2 of 12	1	NM_015117.3	ENSP00000262577.5		Q8IXZ2-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23820

AN:

152214

Hom.:

2190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0637

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.0847

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.174

GnomAD2 exomes

AF:

0.194

AC:

47097

AN:

242712

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.0628

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.0876

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.191

AC:

277957

AN:

1455310

Hom.:

27905

Cov.:

AF XY:

0.193

AC XY:

139503

AN XY:

724226

show subpopulations

African (AFR)

AF:

0.0624

AC:

2088

AN:

33478

American (AMR)

AF:

0.245

AC:

10931

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

6132

AN:

26114

East Asian (EAS)

AF:

0.110

AC:

4369

AN:

39692

South Asian (SAS)

AF:

0.234

AC:

20146

AN:

86200

European-Finnish (FIN)

AF:

0.234

AC:

11099

AN:

47420

Middle Eastern (MID)

AF:

0.253

AC:

1459

AN:

5766

European-Non Finnish (NFE)

AF:

0.189

AC:

210592

AN:

1111704

Other (OTH)

AF:

0.185

AC:

11141

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

16720

33440

50159

66879

83599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7448

14896

22344

29792

37240

<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:

0.156

AC:

23820

AN:

152332

Hom.:

2192

Cov.:

AF XY:

0.160

AC XY:

11912

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0634

AC:

2638

AN:

41590

American (AMR)

AF:

0.187

AC:

2860

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

813

AN:

3472

East Asian (EAS)

AF:

0.0846

AC:

438

AN:

5180

South Asian (SAS)

AF:

0.237

AC:

1143

AN:

4832

European-Finnish (FIN)

AF:

0.234

AC:

2481

AN:

10622

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12765

AN:

68008

Other (OTH)

AF:

0.173

AC:

366

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1042

2084

3125

4167

5209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.177

Hom.:

6715

Bravo

AF:

0.150

TwinsUK

AF:

0.195

AC:

724

ALSPAC

AF:

0.191

AC:

736

ESP6500AA

AF:

0.0640

AC:

281

ESP6500EA

AF:

0.184

AC:

1582

ExAC

AF:

0.189

AC:

22886

Asia WGS

AF:

0.167

AC:

578

AN:

3478

EpiCase

AF:

0.183

EpiControl

AF:

0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

PhyloP100

-0.29

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.12

REVEL

Benign

0.026

Sift

Benign

0.18

Sift4G

Benign

0.76

Polyphen

0.068

Vest4

0.043

ClinPred

0.00082

GERP RS

0.48

Varity_R

0.034

gMVP

0.088

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over