Variant 19-42079142-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000359044.5(ZNF574):c.536T>C(p.Val179Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,613,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

ZNF574
ENST00000359044.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.864

Variant links:

Genes affected

ZNF574 (HGNC:26166): (zinc finger protein 574) 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]

ZNF574 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=0.03653848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF574	NM_022752.6 linkuse as main transcript	c.536T>C	p.Val179Ala	missense_variant	2/2	ENST00000359044.5	NP_073589.4	Q6ZN55-1Q71MF7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF574	ENST00000359044.5 linkuse as main transcript	c.536T>C	p.Val179Ala	missense_variant	2/2	1	NM_022752.6	ENSP00000351939.3	Q6ZN55-1
ZNF574	ENST00000222339.7 linkuse as main transcript	c.806T>C	p.Val269Ala	missense_variant	2/2	3		ENSP00000222339.6	A0A0C4DFM2
ZNF574	ENST00000600245.1 linkuse as main transcript	c.536T>C	p.Val179Ala	missense_variant	2/2	2		ENSP00000469029.1	Q6ZN55-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000332

AC:

AN:

247190

Hom.:

AF XY:

0.000320

AC XY:

AN XY:

134506

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.000784

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.000999

GnomAD4 exome

AF:

0.000287

AC:

419

AN:

1460830

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

200

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000285

Gnomad4 OTH exome

AF:

0.000647

GnomAD4 genome

AF:

0.000282

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000305

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000533

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 09, 2023

The c.536T>C (p.V179A) alteration is located in exon 2 (coding exon 1) of the ZNF574 gene. This alteration results from a T to C substitution at nucleotide position 536, causing the valine (V) at amino acid position 179 to be replaced by an alanine (A). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.016

.;T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.077

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.64

T;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

.;N;N

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.84

N;.;N

REVEL

Benign

0.041

Sift

Benign

0.036

D;.;T

Sift4G

Uncertain

0.053

T;T;T

Polyphen

0.067

.;B;B

Vest4

0.36

MutPred

0.30

.;Loss of stability (P = 0.065);Loss of stability (P = 0.065);

MVP

0.043

MPC

0.50

ClinPred

0.017

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.28

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