2-184936584-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_194250.2(ZNF804A):c.1188C>T(p.Pro396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,613,838 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (27 hom.)
• Consequence: ZNF804A NM_194250.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00600

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-184936584-C-T is Benign according to our data. Variant chr2-184936584-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 770510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.006 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF804A	NM_194250.2	c.1188C>T	p.Pro396=	synonymous_variant	4/4	ENST00000302277.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF804A	ENST00000302277.7	c.1188C>T	p.Pro396=	synonymous_variant	4/4	1	NM_194250.2	P1

Frequencies

GnomAD3 genomes AF: 0.00370 AC: 563 AN: 152014 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00463

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00602

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00354 AC: 887 AN: 250748 Hom.: 2 AF XY: 0.00384 AC XY: 521 AN XY: 135542

Gnomad AFR exome AF: 0.000494

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000849

Gnomad FIN exome AF: 0.00388

Gnomad NFE exome AF: 0.00574

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00452 AC: 6605 AN: 1461708 Hom.: 27 Cov.: 56 AF XY: 0.00454 AC XY: 3300 AN XY: 727142

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.00329

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.00386

Gnomad4 NFE exome AF: 0.00529

Gnomad4 OTH exome AF: 0.00344

GnomAD4 genome AF: 0.00370 AC: 563 AN: 152130 Hom.: 1 Cov.: 32 AF XY: 0.00362 AC XY: 269 AN XY: 74392

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00463

Gnomad4 NFE AF: 0.00600

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00409 Hom.: 0

Bravo AF: 0.00328

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00567

EpiControl AF: 0.00593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	ZNF804A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.3
Dann	Benign	0.31

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

LitVar

Other links and lift over

dbSNP: rs34345078; hg19: chr2-185801311;