2-184598973-A-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_194250.2(ZNF804A):āc.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
NM_194250.2 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 7.99
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]
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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 |
---|---|---|---|---|---|---|---|---|
ZNF804A | NM_194250.2 | c.14A>G | p.Tyr5Cys | missense_variant | 1/4 | ENST00000302277.7 | NP_919226.1 | |
LOC105373780 | NR_171621.1 | n.26T>C | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF804A | ENST00000302277.7 | c.14A>G | p.Tyr5Cys | missense_variant | 1/4 | 1 | NM_194250.2 | ENSP00000303252 | P1 | |
ENST00000640078.1 | n.36T>C | non_coding_transcript_exon_variant | 1/3 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152116Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000435 AC: 109AN: 250508Hom.: 0 AF XY: 0.000398 AC XY: 54AN XY: 135596
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GnomAD4 exome AF: 0.000225 AC: 329AN: 1459492Hom.: 1 Cov.: 30 AF XY: 0.000227 AC XY: 165AN XY: 726208
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GnomAD4 genome AF: 0.000263 AC: 40AN: 152116Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74326
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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 submitter | clinical testing | Ambry Genetics | Feb 17, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at