dbSNP rs3046266: ZNF804A:p.Thr697dup (chr2-184937484-C-CACA) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PM4_SupportingBA1

The NM_194250.2(ZNF804A):c.2090_2092dupCAA(p.Thr697dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,603,270 control chromosomes in the GnomAD database, including 273,085 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 20581 hom., cov: 0)

Exomes 𝑓: 0.58 ( 252504 hom. )

Consequence

ZNF804A
NM_194250.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

7 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 -7 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_194250.2. Strenght limited to Supporting due to length of the change: 1aa.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.2090_2092dupCAA	p.Thr697dup	disruptive_inframe_insertion	Exon 4 of 4	NP_919226.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.2090_2092dupCAA	p.Thr697dup	disruptive_inframe_insertion	Exon 4 of 4	ENSP00000303252.6

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71786

AN:

151652

Hom.:

20582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.592

AC:

143790

AN:

242768

AF XY:

0.591

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.614

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:

843742

AN:

1451498

Hom.:

252504

Cov.:

AF XY:

0.581

AC XY:

419326

AN XY:

722000

show subpopulations

African (AFR)

AF:

0.111

AC:

3694

AN:

33322

American (AMR)

AF:

0.707

AC:

30732

AN:

43498

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

15605

AN:

25634

East Asian (EAS)

AF:

0.844

AC:

33428

AN:

39598

South Asian (SAS)

AF:

0.547

AC:

46446

AN:

84944

European-Finnish (FIN)

AF:

0.640

AC:

33912

AN:

52968

Middle Eastern (MID)

AF:

0.414

AC:

2366

AN:

5714

European-Non Finnish (NFE)

AF:

0.582

AC:

643993

AN:

1105846

Other (OTH)

AF:

0.560

AC:

33566

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

17911

35821

53732

71642

89553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17704

35408

53112

70816

88520

<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:

71787

AN:

151772

Hom.:

20581

Cov.:

AF XY:

0.479

AC XY:

35532

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.133

AC:

5520

AN:

41456

American (AMR)

AF:

0.644

AC:

9814

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2103

AN:

3466

East Asian (EAS)

AF:

0.832

AC:

4281

AN:

5146

South Asian (SAS)

AF:

0.542

AC:

2604

AN:

4808

European-Finnish (FIN)

AF:

0.627

AC:

6571

AN:

10480

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.579

AC:

39296

AN:

67860

Other (OTH)

AF:

0.496

AC:

1043

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1587

3173

4760

6346

7933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.527

Hom.:

3823

Asia WGS

AF:

0.616

AC:

2139

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

Mutation Taster

=81/19

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over