dbSNP rs1366842: ZNF804A:p.Thr707Lys (chr2-184937516-C-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.2120C>A(p.Thr707Lys) 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 1,607,472 control chromosomes in the GnomAD database, including 273,663 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 ( 20719 hom., cov: 33)

Exomes 𝑓: 0.58 ( 252944 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.183

Publications

39 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=8.356307E-7).

BP6

Variant 2-184937516-C-A is Benign according to our data. Variant chr2-184937516-C-A is described in ClinVar as Benign. ClinVar VariationId is 3059400.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2 link	c.2120C>A	p.Thr707Lys	missense_variant	Exon 4 of 4	ENST00000302277.7	NP_919226.1	Q7Z570

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7 link	c.2120C>A	p.Thr707Lys	missense_variant	Exon 4 of 4	1	NM_194250.2	ENSP00000303252.6		Q7Z570

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72074

AN:

151958

Hom.:

20721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.501

GnomAD2 exomes

AF:

0.593

AC:

144400

AN:

243692

AF XY:

0.591

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.615

Gnomad EAS exome

AF:

0.847

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.591

GnomAD4 exome

AF:

0.581

AC:

846302

AN:

1455396

Hom.:

252944

Cov.:

AF XY:

0.581

AC XY:

420564

AN XY:

723870

show subpopulations

African (AFR)

AF:

0.112

AC:

3726

AN:

33368

American (AMR)

AF:

0.707

AC:

30662

AN:

43366

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

15685

AN:

25742

East Asian (EAS)

AF:

0.844

AC:

33428

AN:

39608

South Asian (SAS)

AF:

0.547

AC:

46653

AN:

85292

European-Finnish (FIN)

AF:

0.640

AC:

33945

AN:

53000

Middle Eastern (MID)

AF:

0.415

AC:

2372

AN:

5720

European-Non Finnish (NFE)

AF:

0.583

AC:

646173

AN:

1109176

Other (OTH)

AF:

0.560

AC:

33658

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

18697

37394

56090

74787

93484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17784

35568

53352

71136

88920

<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:

0.474

AC:

72073

AN:

152076

Hom.:

20719

Cov.:

AF XY:

0.480

AC XY:

35700

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.134

AC:

5541

AN:

41488

American (AMR)

AF:

0.644

AC:

9840

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2107

AN:

3466

East Asian (EAS)

AF:

0.833

AC:

4304

AN:

5166

South Asian (SAS)

AF:

0.542

AC:

2615

AN:

4824

European-Finnish (FIN)

AF:

0.629

AC:

6643

AN:

10558

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.580

AC:

39418

AN:

67966

Other (OTH)

AF:

0.497

AC:

1049

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1603

3205

4808

6410

8013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.551

Hom.:

56273

Bravo

AF:

0.465

TwinsUK

AF:

0.586

AC:

2172

ALSPAC

AF:

0.603

AC:

2323

ESP6500AA

AF:

0.140

AC:

615

ESP6500EA

AF:

0.577

AC:

4953

ExAC

AF:

0.575

AC:

69820

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF804A-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.092

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.9

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

8.4e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

L;.

PhyloP100

0.18

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.21

N;.

REVEL

Benign

0.018

Sift

Benign

1.0

T;.

Sift4G

Benign

0.97

T;T

Polyphen

0.0020

B;.

Vest4

0.026

MPC

0.28

ClinPred

0.0059

GERP RS

1.9

Varity_R

0.022

gMVP

0.11

Mutation Taster

=99/1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over