dbSNP rs1366842: ZNF804A:p.Thr707Lys (chr2-184937516-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.47 ( 20719 hom., cov: 33)

Exomes 𝑓: 0.58 ( 252944 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.183

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2 link	c.2120C>A	p.Thr707Lys	missense_variant	Exon 4 of 4	ENST00000302277.7	NP_919226.1	Q7Z570

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7 link	c.2120C>A	p.Thr707Lys	missense_variant	Exon 4 of 4	1	NM_194250.2	ENSP00000303252.6		Q7Z570

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72074

AN:

151958

Hom.:

20721

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.593

AC:

144400

AN:

243692

Hom.:

45977

AF XY:

0.591

AC XY:

78077

AN XY:

132160

show subpopulations

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 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:

846302

AN:

1455396

Hom.:

252944

Cov.:

AF XY:

0.581

AC XY:

420564

AN XY:

723870

show subpopulations

Gnomad4 AFR exome

AF:

0.112

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:

0.583

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.474

AC:

72073

AN:

152076

Hom.:

20719

Cov.:

AF XY:

0.480

AC XY:

35700

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.644

Gnomad4 ASJ

AF:

0.608

Gnomad4 EAS

AF:

0.833

Gnomad4 SAS

AF:

0.542

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.580

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.573

Hom.:

38880

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF804A-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.9

DANN

Benign

0.15

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

8.4e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.21

N;.

REVEL

Benign

0.018

Sift

Benign

1.0

T;.

Sift4G

Benign

0.97

T;T

Polyphen

0.0020

B;.

Vest4

0.026

MPC

0.28

ClinPred

0.0059

GERP RS

1.9

Varity_R

0.022

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over