dbSNP rs4667001: ZNF804A:p.Glu542Lys (chr2-184937020-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_194250.2(ZNF804A):c.1624G>A(p.Glu542Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,612,128 control chromosomes in the GnomAD database, including 274,003 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.47 ( 20580 hom., cov: 31)

Exomes 𝑓: 0.58 ( 253423 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.56

Publications

36 publications found

Variant links:

Genes affected

ZNF804A (HGNC:21711): (zinc finger protein 804A) The protein encoded by this gene is a zinc finger binding protein. Polymorphisms in this gene, especially rs1344706, are thought to confer increased susceptibility to schizophrenia, bipolar disorder, and heroin addiciton. [provided by RefSeq, Nov 2015]

ZNF804A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ZNF804A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0094146E-6).

BP6

Variant 2-184937020-G-A is Benign according to our data. Variant chr2-184937020-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059275.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194250.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.1624G>A	p.Glu542Lys	missense	Exon 4 of 4	NP_919226.1	Q7Z570

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.1624G>A	p.Glu542Lys	missense	Exon 4 of 4	ENSP00000303252.6	Q7Z570

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71764

AN:

151584

Hom.:

20583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.643

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.831

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.501

GnomAD2 exomes

AF:

0.594

AC:

147519

AN:

248450

AF XY:

0.591

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.717

Gnomad ASJ exome

AF:

0.616

Gnomad EAS exome

AF:

0.846

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.594

GnomAD4 exome

AF:

0.582

AC:

849304

AN:

1460426

Hom.:

253423

Cov.:

AF XY:

0.581

AC XY:

422100

AN XY:

726474

show subpopulations

African (AFR)

AF:

0.113

AC:

3771

AN:

33436

American (AMR)

AF:

0.708

AC:

31492

AN:

44476

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

15901

AN:

26062

East Asian (EAS)

AF:

0.844

AC:

33426

AN:

39602

South Asian (SAS)

AF:

0.548

AC:

47173

AN:

86144

European-Finnish (FIN)

AF:

0.641

AC:

34182

AN:

53366

Middle Eastern (MID)

AF:

0.416

AC:

2392

AN:

5754

European-Non Finnish (NFE)

AF:

0.582

AC:

647194

AN:

1111276

Other (OTH)

AF:

0.560

AC:

33773

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

18040

36081

54121

72162

90202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17806

35612

53418

71224

89030

<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:

0.473

AC:

71762

AN:

151702

Hom.:

20580

Cov.:

AF XY:

0.479

AC XY:

35497

AN XY:

74104

show subpopulations

African (AFR)

AF:

0.133

AC:

5516

AN:

41428

American (AMR)

AF:

0.643

AC:

9803

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2097

AN:

3462

East Asian (EAS)

AF:

0.831

AC:

4277

AN:

5146

South Asian (SAS)

AF:

0.543

AC:

2612

AN:

4814

European-Finnish (FIN)

AF:

0.626

AC:

6568

AN:

10484

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.579

AC:

39293

AN:

67822

Other (OTH)

AF:

0.497

AC:

1046

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1552

3103

4655

6206

7758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.533

Hom.:

42929

Bravo

AF:

0.465

TwinsUK

AF:

0.586

AC:

2172

ALSPAC

AF:

0.603

AC:

2323

ESP6500AA

AF:

0.140

AC:

603

ESP6500EA

AF:

0.577

AC:

4940

ExAC

AF:

0.576

AC:

69820

Asia WGS

AF:

0.615

AC:

2136

AN:

3474

EpiCase

AF:

0.577

EpiControl

AF:

0.584

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ZNF804A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

1.6

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.5

REVEL

Benign

0.038

Sift

Benign

0.11

Sift4G

Benign

0.22

Polyphen

0.012

Vest4

0.025

MPC

0.039

ClinPred

0.0025

GERP RS

3.2

Varity_R

0.093

gMVP

0.11

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over