Variant chr19-42079324-C-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_022752.6(ZNF574):c.718C>T(p.Pro240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF574
NM_022752.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

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:

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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=0.05074531).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF574	NM_022752.6 link	c.718C>T	p.Pro240Ser	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 link	c.718C>T	p.Pro240Ser	missense_variant	2/2	1	NM_022752.6	ENSP00000351939.3	Q6ZN55-1
ZNF574	ENST00000222339.7 link	c.988C>T	p.Pro330Ser	missense_variant	2/2	3		ENSP00000222339.6	A0A0C4DFM2
ZNF574	ENST00000600245.1 link	c.718C>T	p.Pro240Ser	missense_variant	2/2	2		ENSP00000469029.1	Q6ZN55-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 29, 2021

The c.718C>T (p.P240S) alteration is located in exon 2 (coding exon 1) of the ZNF574 gene. This alteration results from a C to T substitution at nucleotide position 718, causing the proline (P) at amino acid position 240 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.4

DANN

Benign

0.91

DEOGEN2

Benign

0.010

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.64

T;.;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

.;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.080

N;.;N

REVEL

Benign

0.0080

Sift

Benign

0.35

T;.;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.0040

.;B;B

Vest4

0.16

MutPred

0.22

.;Gain of phosphorylation at P240 (P = 0.0637);Gain of phosphorylation at P240 (P = 0.0637);

MVP

0.043

MPC

0.42

ClinPred

0.083

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

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