Variant chr2-184936178-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_194250.2(ZNF804A):c.782A>T(p.Gln261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 1,613,750 control chromosomes in the GnomAD database, including 322,495 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.60 ( 28002 hom., cov: 32)

Exomes 𝑓: 0.63 ( 294493 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.151

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1170101E-6).

BP6

Variant 2-184936178-A-T is Benign according to our data. Variant chr2-184936178-A-T is described in ClinVar as [Benign]. Clinvar id is 1221151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF804A	NM_194250.2 linkuse as main transcript	c.782A>T	p.Gln261Leu	missense_variant	4/4	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7 linkuse as main transcript	c.782A>T	p.Gln261Leu	missense_variant	4/4	1	NM_194250.2	ENSP00000303252	P1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

90997

AN:

151928

Hom.:

27995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.831

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.619

GnomAD3 exomes

AF:

0.656

AC:

164749

AN:

251092

Hom.:

55061

AF XY:

0.653

AC XY:

88576

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.756

Gnomad ASJ exome

AF:

0.704

Gnomad EAS exome

AF:

0.842

Gnomad SAS exome

AF:

0.624

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.625

Gnomad OTH exome

AF:

0.657

GnomAD4 exome

AF:

0.632

AC:

924106

AN:

1461704

Hom.:

294493

Cov.:

AF XY:

0.632

AC XY:

459796

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.457

Gnomad4 AMR exome

AF:

0.750

Gnomad4 ASJ exome

AF:

0.695

Gnomad4 EAS exome

AF:

0.850

Gnomad4 SAS exome

AF:

0.628

Gnomad4 FIN exome

AF:

0.663

Gnomad4 NFE exome

AF:

0.623

Gnomad4 OTH exome

AF:

0.626

GnomAD4 genome

AF:

0.599

AC:

91041

AN:

152046

Hom.:

28002

Cov.:

AF XY:

0.603

AC XY:

44784

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.465

Gnomad4 AMR

AF:

0.710

Gnomad4 ASJ

AF:

0.704

Gnomad4 EAS

AF:

0.831

Gnomad4 SAS

AF:

0.619

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.624

Gnomad4 OTH

AF:

0.612

Alfa

AF:

0.629

Hom.:

22845

Bravo

AF:

0.601

TwinsUK

AF:

0.622

AC:

2307

ALSPAC

AF:

0.642

AC:

2474

ESP6500AA

AF:

0.479

AC:

2109

ESP6500EA

AF:

0.629

AC:

5404

ExAC

AF:

0.645

AC:

78267

Asia WGS

AF:

0.666

AC:

2316

AN:

3478

EpiCase

AF:

0.624

EpiControl

AF:

0.634

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2020	This variant is associated with the following publications: (PMID: 24315717) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

DANN

Benign

0.94

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.024

T;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.8

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.73

N;.

REVEL

Benign

0.062

Sift

Benign

0.37

T;.

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;.

Vest4

0.018

MPC

0.035

ClinPred

0.0039

GERP RS

0.19

Varity_R

0.062

gMVP

0.066

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