rs3046266

chr2-184937484-C-CACA

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PM4_Supporting BA1

The NM_194250.2(ZNF804A):c.2090_2092dup(p.Thr697dup) variant causes a 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 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZNF804A	NM_194250.2	c.2090_2092dup	p.Thr697dup	inframe_insertion	4/4	ENST00000302277.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF804A	ENST00000302277.7	c.2090_2092dup	p.Thr697dup	inframe_insertion	4/4	1	NM_194250.2	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71786 AN: 151652 Hom.: 20582 Cov.: 0

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

GnomAD3 exomes AF: 0.592 AC: 143790 AN: 242768 Hom.: 45868 AF XY: 0.591 AC XY: 77704 AN XY: 131578

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 SAS exome AF: 0.541

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.: 41 AF XY: 0.581 AC XY: 419326 AN XY: 722000

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.473 AC: 71787 AN: 151772 Hom.: 20581 Cov.: 0 AF XY: 0.479 AC XY: 35532 AN XY: 74172

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.496

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3046266; hg19: chr2-185802211;