chr18-14124370-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_145287.4(ZNF519):c.110A>G(p.Tyr37Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000802 in 1,608,776 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 (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000080 ( 1 hom. )
Consequence
ZNF519
NM_145287.4 missense
NM_145287.4 missense
Scores
3
11
Clinical Significance
Conservation
PhyloP100: 0.713
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 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=0.053299397).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF519 | NM_145287.4 | c.110A>G | p.Tyr37Cys | missense_variant | 2/3 | ENST00000590202.3 | |
ZNF519 | NR_033354.2 | n.161+7905A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF519 | ENST00000590202.3 | c.110A>G | p.Tyr37Cys | missense_variant | 2/3 | 1 | NM_145287.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152056Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000142 AC: 35AN: 246968Hom.: 0 AF XY: 0.000120 AC XY: 16AN XY: 133584
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GnomAD4 exome AF: 0.0000803 AC: 117AN: 1456720Hom.: 1 Cov.: 30 AF XY: 0.0000828 AC XY: 60AN XY: 724564
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GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74266
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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 14, 2023 | The c.110A>G (p.Y37C) alteration is located in exon 2 (coding exon 2) of the ZNF519 gene. This alteration results from a A to G substitution at nucleotide position 110, causing the tyrosine (Y) at amino acid position 37 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
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Polyphen
0.0040
.;B
Vest4
MutPred
Loss of stability (P = 0.1776);Loss of stability (P = 0.1776);
MVP
MPC
0.012
ClinPred
T
RBP_binding_hub_radar
RBP_regulation_power_radar
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