Variant 19-12430299-A-T 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_005815.5(ZNF443):c.1873T>A(p.Phe625Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,612,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF443
NM_005815.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

ZNF443 (HGNC:20878): (zinc finger protein 443) Zinc finger proteins (ZNFs) bind DNA and, through this binding, regulate gene transcription. Most ZNFs contain conserved C2H2 motifs and are classified as Kruppel-type zinc fingers. For a general description of these proteins, see ZNF91 (MIM 603971).[supplied by OMIM, Jul 2002]

ZNF443 links:

ENSG00000268870 (HGNC:):

ENSG00000268870 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=0.0261769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF443	NM_005815.5 linkuse as main transcript	c.1873T>A	p.Phe625Ile	missense_variant	4/4	ENST00000301547.10	NP_005806.3	Q9Y2A4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF443	ENST00000301547.10 linkuse as main transcript	c.1873T>A	p.Phe625Ile	missense_variant	4/4	1	NM_005815.5	ENSP00000301547.5		Q9Y2A4
ENSG00000268870	ENST00000595562.1 linkuse as main transcript	c.3+10613T>A		intron_variant		4		ENSP00000471613.1		M0R135

Frequencies

GnomAD3 genomes

AF:

0.000251

AC:

AN:

151212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.0000919

AC:

AN:

250392

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000899

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

162

AN:

1461312

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00219

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000783

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000251

AC:

AN:

151212

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73744

show subpopulations

Gnomad4 AFR

AF:

0.0000730

Gnomad4 AMR

AF:

0.000264

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.000424

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000119

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 03, 2023

The c.1873T>A (p.F625I) alteration is located in exon 4 (coding exon 4) of the ZNF443 gene. This alteration results from a T to A substitution at nucleotide position 1873, causing the phenylalanine (F) at amino acid position 625 to be replaced by an isoleucine (I). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.064

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.50

M_CAP

Benign

0.0025

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.80

MutationAssessor

Pathogenic

3.4

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.11

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.094

Vest4

0.38

MVP

0.46

MPC

0.081

ClinPred

0.22

GERP RS

1.3

Varity_R

0.33

gMVP

0.064

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