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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2 link	c.2090_2092dupCAA	p.Thr697dup	disruptive_inframe_insertion	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.2090_2092dupCAA	p.Thr697dup	disruptive_inframe_insertion	Exon 4 of 4	1	NM_194250.2	ENSP00000303252.6		Q7Z570

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

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

Alfa

AF:

0.527

Hom.:

3823

Asia WGS

AF:

0.616

AC:

2139

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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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rs3046266

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