Variant 19-42078910-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022752.6(ZNF574):c.304A>C(p.Met102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,613,904 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

ZNF574
NM_022752.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.917

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035008132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF574	NM_022752.6 linkuse as main transcript	c.304A>C	p.Met102Leu	missense_variant	2/2	ENST00000359044.5	NP_073589.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF574	ENST00000359044.5 linkuse as main transcript	c.304A>C	p.Met102Leu	missense_variant	2/2	1	NM_022752.6	ENSP00000351939	P1	Q6ZN55-1
ZNF574	ENST00000222339.7 linkuse as main transcript	c.574A>C	p.Met192Leu	missense_variant	2/2	3		ENSP00000222339
ZNF574	ENST00000600245.1 linkuse as main transcript	c.304A>C	p.Met102Leu	missense_variant	2/2	2		ENSP00000469029	P1	Q6ZN55-1
ZNF574	ENST00000597391.1 linkuse as main transcript	c.304A>C	p.Met102Leu	missense_variant	3/3	4		ENSP00000471611

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000545

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000327

AC:

AN:

251136

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000573

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000445

AC:

650

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

329

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000541

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000276

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000545

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000508

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000593

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 06, 2021

The c.304A>C (p.M102L) alteration is located in exon 2 (coding exon 1) of the ZNF574 gene. This alteration results from a A to C substitution at nucleotide position 304, causing the methionine (M) at amino acid position 102 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0094

.;T;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.57

T;.;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.035

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.;N

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.080

N;.;.;N

REVEL

Benign

0.065

Sift

Benign

1.0

T;.;.;T

Sift4G

Benign

0.59

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.35

MutPred

0.27

.;Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);

MVP

0.082

MPC

0.38

ClinPred

0.017

GERP RS

2.3

Varity_R

0.092

gMVP

0.079

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