2-184598973-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_194250.2(ZNF804A):ā€‹c.14A>Gā€‹(p.Tyr5Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,611,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00026 ( 0 hom., cov: 33)
Exomes š‘“: 0.00023 ( 1 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.013999373).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF804ANM_194250.2 linkuse as main transcriptc.14A>G p.Tyr5Cys missense_variant 1/4 ENST00000302277.7 NP_919226.1
LOC105373780NR_171621.1 linkuse as main transcriptn.26T>C non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF804AENST00000302277.7 linkuse as main transcriptc.14A>G p.Tyr5Cys missense_variant 1/41 NM_194250.2 ENSP00000303252 P1
ENST00000640078.1 linkuse as main transcriptn.36T>C non_coding_transcript_exon_variant 1/35

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152116
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00952
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000435
AC:
109
AN:
250508
Hom.:
0
AF XY:
0.000398
AC XY:
54
AN XY:
135596
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00955
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000886
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000225
AC:
329
AN:
1459492
Hom.:
1
Cov.:
30
AF XY:
0.000227
AC XY:
165
AN XY:
726208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00957
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.000597
GnomAD4 genome
AF:
0.000263
AC:
40
AN:
152116
Hom.:
0
Cov.:
33
AF XY:
0.000202
AC XY:
15
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00952
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000486
Hom.:
0
Bravo
AF:
0.000280
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000305
AC:
37
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 17, 2022The c.14A>G (p.Y5C) alteration is located in exon 1 (coding exon 1) of the ZNF804A gene. This alteration results from a A to G substitution at nucleotide position 14, causing the tyrosine (Y) at amino acid position 5 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.034
T
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.043
T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.014
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-3.4
D
REVEL
Uncertain
0.44
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.72
MVP
0.21
MPC
0.26
ClinPred
0.35
T
GERP RS
4.1
Varity_R
0.53
gMVP
0.89

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.

Other links and lift over

dbSNP: rs149912547; hg19: chr2-185463700; COSMIC: COSV56435075; API