rs61739291

Positions:

• chr2-184936376-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_194250.2(ZNF804A):​c.980A>C​(p.Asn327Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,614,010 control chromosomes in the GnomAD database, including 691 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (49 hom., cov: 33)
  • Exomes 𝑓: 0.028 (642 hom.)
• Consequence: ZNF804A NM_194250.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002303481).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.019 (2887/152312) while in subpopulation NFE AF= 0.0287 (1949/68010). AF 95% confidence interval is 0.0276. There are 49 homozygotes in gnomad4. There are 1352 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 49 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF804A	NM_194250.2	c.980A>C	p.Asn327Thr	missense_variant	4/4	ENST00000302277.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF804A	ENST00000302277.7	c.980A>C	p.Asn327Thr	missense_variant	4/4	1	NM_194250.2	P1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2886 AN: 152194 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.00596

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.0196 AC: 4889 AN: 249558 Hom.: 68 AF XY: 0.0201 AC XY: 2715 AN XY: 135004

Gnomad AFR exome AF: 0.00460

Gnomad AMR exome AF: 0.00748

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0178

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0273

Gnomad OTH exome AF: 0.0205

GnomAD4 exome AF: 0.0277 AC: 40454 AN: 1461698 Hom.: 642 Cov.: 57 AF XY: 0.0273 AC XY: 19841 AN XY: 727134

Gnomad4 AFR exome AF: 0.00394

Gnomad4 AMR exome AF: 0.00799

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0190

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.0313

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0190 AC: 2887 AN: 152312 Hom.: 49 Cov.: 33 AF XY: 0.0182 AC XY: 1352 AN XY: 74478

Gnomad4 AFR AF: 0.00594

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0287

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0261 Hom.: 79

Bravo AF: 0.0174

TwinsUK AF: 0.0305 AC: 113

ALSPAC AF: 0.0371 AC: 143

ESP6500AA AF: 0.00681 AC: 30

ESP6500EA AF: 0.0271 AC: 233

ExAC AF: 0.0194 AC: 2353

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0242

EpiControl AF: 0.0264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.1
DANN	Benign	0.97
DEOGEN2	Benign	0.0051	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.68	T;T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.022
Sift	Benign	0.30	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.14	B;.
Vest4		0.032
MPC		0.050
ClinPred		0.0053	T
GERP RS		3.1
Varity_R		0.065
gMVP		0.072

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: rs61739291; hg19: chr2-185801103;