Genetic Variant NM_014518.4:c.1984G>A (chr19-44428797-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014518.4(ZNF229):c.1984G>A(p.Gly662Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,830 control chromosomes in the GnomAD database, including 94,425 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6667 hom., cov: 32)

Exomes 𝑓: 0.34 ( 87758 hom. )

Consequence

ZNF229
NM_014518.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

Publications

41 publications found

Variant links:

Genes affected

ZNF229 (HGNC:13022): (zinc finger protein 229) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF229 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ZNF229 links:

ENSG00000267188 (HGNC:):

ENSG00000267188 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=8.544326E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF229	NM_014518.4 link	c.1984G>A	p.Gly662Arg	missense_variant	Exon 6 of 6	ENST00000614049.5	NP_055333.3	Q9UJW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF229	ENST00000614049.5 link	c.1984G>A	p.Gly662Arg	missense_variant	Exon 6 of 6	1	NM_014518.4	ENSP00000479884.1		Q9UJW7-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40929

AN:

151846

Hom.:

6670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0942

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.303

GnomAD2 exomes

AF:

0.326

AC:

81535

AN:

249944

AF XY:

0.341

show subpopulations

Gnomad AFR exome

AF:

0.0884

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.341

AC:

498794

AN:

1461866

Hom.:

87758

Cov.:

AF XY:

0.347

AC XY:

252029

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0825

AC:

2763

AN:

33476

American (AMR)

AF:

0.263

AC:

11770

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8379

AN:

26136

East Asian (EAS)

AF:

0.345

AC:

13682

AN:

39686

South Asian (SAS)

AF:

0.465

AC:

40071

AN:

86258

European-Finnish (FIN)

AF:

0.332

AC:

17757

AN:

53418

Middle Eastern (MID)

AF:

0.317

AC:

1830

AN:

5768

European-Non Finnish (NFE)

AF:

0.344

AC:

382534

AN:

1112004

Other (OTH)

AF:

0.331

AC:

20008

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

23930

47860

71791

95721

119651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12280

24560

36840

49120

61400

<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:

0.269

AC:

40930

AN:

151964

Hom.:

6667

Cov.:

AF XY:

0.272

AC XY:

20236

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0941

AC:

3899

AN:

41442

American (AMR)

AF:

0.275

AC:

4204

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1148

AN:

3464

East Asian (EAS)

AF:

0.330

AC:

1697

AN:

5140

South Asian (SAS)

AF:

0.467

AC:

2249

AN:

4818

European-Finnish (FIN)

AF:

0.342

AC:

3615

AN:

10558

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22977

AN:

67958

Other (OTH)

AF:

0.303

AC:

639

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1440

2879

4319

5758

7198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.318

Hom.:

27596

Bravo

AF:

0.254

TwinsUK

AF:

0.342

AC:

1267

ALSPAC

AF:

0.331

AC:

1276

ESP6500AA

AF:

0.0911

AC:

393

ESP6500EA

AF:

0.341

AC:

2912

ExAC

AF:

0.324

AC:

39230

Asia WGS

AF:

0.353

AC:

1228

AN:

3478

EpiCase

AF:

0.354

EpiControl

AF:

0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.083

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.85

T;.

MetaRNN

Benign

0.00085

T;T

MetaSVM

Benign

-1.1

PhyloP100

1.7

PrimateAI

Uncertain

0.49

Sift4G

Uncertain

0.011

D;D

Vest4

0.091

MutPred

0.64

.;Gain of MoRF binding (P = 0.0186);

ClinPred

0.037

GERP RS

3.5

gMVP

0.053

Mutation Taster

=97/3

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

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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