chr18-14105731-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145287.4(ZNF519):c.809G>A(p.Arg270His) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
ZNF519
NM_145287.4 missense
NM_145287.4 missense
Scores
1
2
13
Clinical Significance
Conservation
PhyloP100: 3.93
Genes affected
ZNF519 (HGNC:30574): (zinc finger protein 519) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08667651).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF519 | NM_145287.4 | c.809G>A | p.Arg270His | missense_variant | 3/3 | ENST00000590202.3 | |
ZNF519 | NR_033354.2 | n.162-20655G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF519 | ENST00000590202.3 | c.809G>A | p.Arg270His | missense_variant | 3/3 | 1 | NM_145287.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152162Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250298Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135432
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461586Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5AN XY: 727078
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152280Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74460
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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 | Oct 02, 2023 | The c.809G>A (p.R270H) alteration is located in exon 3 (coding exon 3) of the ZNF519 gene. This alteration results from a G to A substitution at nucleotide position 809, causing the arginine (R) at amino acid position 270 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MutPred
Loss of MoRF binding (P = 0.0269);
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