19-37127822-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_144689.5(ZNF420):āc.831G>Cā(p.Lys277Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000040 ( 0 hom., cov: 33)
Exomes š: 0.000039 ( 0 hom. )
Consequence
ZNF420
NM_144689.5 missense
NM_144689.5 missense
Scores
4
3
11
Clinical Significance
Conservation
PhyloP100: -0.841
Genes affected
ZNF420 (HGNC:20649): (zinc finger protein 420) The protein encoded by this gene is a KRAB-type zinc finger protein that negatively-regulates p53-mediated apoptosis. Under stress conditions, the encoded protein is phosphorylated by ATM and dissociates from p53, which activates p53 and initiates apoptosis. [provided by RefSeq, Jul 2016]
ZNF585A (HGNC:26305): (zinc finger protein 585A) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active 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=0.18978846).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF420 | NM_144689.5 | c.831G>C | p.Lys277Asn | missense_variant | 5/5 | ENST00000337995.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF420 | ENST00000337995.4 | c.831G>C | p.Lys277Asn | missense_variant | 5/5 | 1 | NM_144689.5 | P1 | |
ZNF420 | ENST00000304239.11 | c.831G>C | p.Lys277Asn | missense_variant | 5/6 | 2 | |||
ZNF585A | ENST00000587817.5 | c.338-12657C>G | intron_variant, NMD_transcript_variant | 2 | |||||
ZNF585A | ENST00000588723.5 | n.503-12657C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151798Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250790Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135636
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GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461744Hom.: 0 Cov.: 32 AF XY: 0.0000371 AC XY: 27AN XY: 727162
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 151798Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74122
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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 | May 25, 2022 | The c.831G>C (p.K277N) alteration is located in exon 5 (coding exon 3) of the ZNF420 gene. This alteration results from a G to C substitution at nucleotide position 831, causing the lysine (K) at amino acid position 277 to be replaced by an asparagine (N). 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MutPred
Loss of methylation at K277 (P = 0.0067);Loss of methylation at K277 (P = 0.0067);
MVP
MPC
0.97
ClinPred
D
GERP RS
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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