Variant chr19-36719952-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001322917.1(ZNF567):c.1228G>C(p.Val410Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,613,868 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

ZNF567
NM_001322917.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.942

Variant links:

Genes affected

ZNF567 (HGNC:28696): (zinc finger protein 567) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF567 links:

ZNF850 (HGNC:27994): (zinc finger protein 850) 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]

ZNF850 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.098840594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF567	NM_001322917.1 linkuse as main transcript	c.1228G>C	p.Val410Leu	missense_variant	6/6	ENST00000682579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF567	ENST00000682579.1 linkuse as main transcript	c.1228G>C	p.Val410Leu	missense_variant	6/6		NM_001322917.1	P1	Q8N184-3

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

250648

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000133

AC:

195

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

110

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000158

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000117

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Dec 21, 2022

The c.1135G>C (p.V379L) alteration is located in exon 4 (coding exon 3) of the ZNF567 gene. This alteration results from a G to C substitution at nucleotide position 1135, causing the valine (V) at amino acid position 379 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

Pathogenic

0.82

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.025

T;.;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.00058

LIST_S2

Benign

0.46

T;.;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.12

N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.3

N;N;.;.

REVEL

Benign

0.058

Sift

Benign

0.30

T;T;.;.

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.014

B;.;B;.

Vest4

0.15

MutPred

0.29

Loss of methylation at K405 (P = 0.0727);.;.;.;

MVP

0.51

MPC

0.56

ClinPred

0.085

GERP RS

3.0

Varity_R

0.050

gMVP

0.18

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