NM_194250.2:c.2120C>A

Variant names:

• chr2-184937516-C-A
• rs1366842
• NM_194250.2:c.2120C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.183
• Publications: 39 publications found

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

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.2120C>A	p.Thr707Lys	missense	Exon 4 of 4	NP_919226.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.2120C>A	p.Thr707Lys	missense	Exon 4 of 4	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72074 AN: 151958 Hom.: 20721 Cov.: 33

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

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.: 43 AF XY: 0.581 AC XY: 420564 AN XY: 723870

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

GnomAD4 genome AF: 0.474 AC: 72073 AN: 152076 Hom.: 20719 Cov.: 33 AF XY: 0.480 AC XY: 35700 AN XY: 74350

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

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ZNF804A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.15
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	8.4e-7	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.18
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	0.97	T
Polyphen		0.0020	B
Vest4		0.026
MPC		0.28
ClinPred		0.0059	T
GERP RS		1.9
Varity_R		0.022
gMVP		0.11
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1366842; hg19: chr2-185802243; COSMIC: COSV56451912;