Variant 19-37127248-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144689.5(ZNF420):c.257C>G(p.Ser86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF420
NM_144689.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.31

Variant links:

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]

ZNF420 links:

ENSG00000267360 (HGNC:):

ENSG00000267360 links:

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]

ZNF585A links:

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=0.06273052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF420	NM_144689.5 linkuse as main transcript	c.257C>G	p.Ser86Cys	missense_variant	5/5	ENST00000337995.4	NP_653290.2	Q8TAQ5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF420	ENST00000337995.4 linkuse as main transcript	c.257C>G	p.Ser86Cys	missense_variant	5/5	1	NM_144689.5	ENSP00000338770.2		Q8TAQ5-1
ENSG00000267360	ENST00000588873.1 linkuse as main transcript	c.253+28617G>C		intron_variant		5		ENSP00000465212.1		K7EJK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250536

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461234

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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

Jul 02, 2024

The c.257C>G (p.S86C) alteration is located in exon 5 (coding exon 3) of the ZNF420 gene. This alteration results from a C to G substitution at nucleotide position 257, causing the serine (S) at amino acid position 86 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

Benign

0.066

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.3

DANN

Benign

0.54

DEOGEN2

Benign

0.013

T;.;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.71

T;T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.063

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

.;.;N;.;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.13

.;.;N;.;N

REVEL

Benign

0.0030

Sift

Benign

0.18

.;.;T;.;T

Sift4G

Benign

0.19

T;T;T;T;T

Polyphen

0.19

.;.;.;.;B

Vest4

0.17, 0.15

MutPred

0.27

.;Loss of phosphorylation at S86 (P = 0.019);Loss of phosphorylation at S86 (P = 0.019);Loss of phosphorylation at S86 (P = 0.019);Loss of phosphorylation at S86 (P = 0.019);

MVP

0.055

MPC

0.81

ClinPred

0.040

GERP RS

1.5

Varity_R

0.048

gMVP

0.047

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over