rs61739291

Variant names:

• chr2-184936376-A-C
• rs61739291
• NM_194250.2:c.980A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000302277.7(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. 15/21 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 ENST00000302277.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 9 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 -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2887 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000302277.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.980A>C	p.Asn327Thr	missense	Exon 4 of 4	NP_919226.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.980A>C	p.Asn327Thr	missense	Exon 4 of 4	ENSP00000303252.6

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

GnomAD2 exomes AF: 0.0196 AC: 4889 AN: 249558 AF XY: 0.0201

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 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

African (AFR) AF: 0.00394 AC: 132 AN: 33478

American (AMR) AF: 0.00799 AC: 357 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 553 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39662

South Asian (SAS) AF: 0.0190 AC: 1635 AN: 86252

European-Finnish (FIN) AF: 0.0272 AC: 1454 AN: 53408

Middle Eastern (MID) AF: 0.00937 AC: 54 AN: 5764

European-Non Finnish (NFE) AF: 0.0313 AC: 34786 AN: 1111938

Other (OTH) AF: 0.0245 AC: 1479 AN: 60386

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

African (AFR) AF: 0.00594 AC: 247 AN: 41588

American (AMR) AF: 0.0107 AC: 163 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4828

European-Finnish (FIN) AF: 0.0299 AC: 317 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1949 AN: 68010

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0257 Hom.: 168

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 v4.9

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
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.079
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.022
Sift	Benign	0.30	T
Sift4G	Benign	0.22	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
Mutation Taster		=97/3	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: rs61739291; hg19: chr2-185801103;