Variant 19-37127229-G-A 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.238G>A(p.Asp80Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,457,358 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF420
NM_144689.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.186

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:

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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=0.03435868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF420	NM_144689.5 linkuse as main transcript	c.238G>A	p.Asp80Asn	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.238G>A	p.Asp80Asn	missense_variant	5/5	1	NM_144689.5	ENSP00000338770.2		Q8TAQ5-1
ENSG00000267360	ENST00000588873.1 linkuse as main transcript	c.253+28636C>T		intron_variant		5		ENSP00000465212.1		K7EJK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

246686

Hom.:

AF XY:

0.0000375

AC XY:

AN XY:

133344

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000439

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1457358

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724732

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000530

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Mar 16, 2024

The c.238G>A (p.D80N) alteration is located in exon 5 (coding exon 3) of the ZNF420 gene. This alteration results from a G to A substitution at nucleotide position 238, causing the aspartic acid (D) at amino acid position 80 to be replaced by an asparagine (N). 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

0.071

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.0062

T;.;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.70

T;T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.034

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.0

.;.;L;.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

0.40

.;.;N;.;N

REVEL

Benign

0.039

Sift

Benign

0.36

.;.;T;.;T

Sift4G

Benign

0.92

T;T;T;T;T

Polyphen

0.0

.;.;.;.;B

Vest4

0.19, 0.16

MutPred

0.26

.;Gain of catalytic residue at D80 (P = 0.0774);Gain of catalytic residue at D80 (P = 0.0774);Gain of catalytic residue at D80 (P = 0.0774);Gain of catalytic residue at D80 (P = 0.0774);

MVP

0.13

MPC

0.68

ClinPred

0.018

GERP RS

0.13

Varity_R

0.038

gMVP

0.035

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