Variant 19-36950069-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198539.4(ZNF568):c.916T>A(p.Tyr306Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF568
NM_198539.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF568 links:

ENSG00000291239 (HGNC:):

ENSG00000291239 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_198539.4 linkuse as main transcript	c.916T>A	p.Tyr306Asn	missense_variant	7/7	ENST00000333987.12	NP_940941.2	Q3ZCX4-1Q96AZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF568	ENST00000333987.12 linkuse as main transcript	c.916T>A	p.Tyr306Asn	missense_variant	7/7	1	NM_198539.4	ENSP00000334685.7		Q3ZCX4-1
ENSG00000291239	ENST00000706165.1 linkuse as main transcript	c.358+12827T>A		intron_variant				ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249696

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

AF:

0.00000137

AC:

AN:

1461588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

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

Jun 28, 2024

The c.916T>A (p.Y306N) alteration is located in exon 7 (coding exon 5) of the ZNF568 gene. This alteration results from a T to A substitution at nucleotide position 916, causing the tyrosine (Y) at amino acid position 306 to be replaced by an asparagine (N). 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

0.84

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;.;.;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

-0.037

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.92

.;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.45

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;.;.;M;.

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-8.1

D;D;.;.;.

REVEL

Benign

0.080

Sift

Pathogenic

0.0

D;D;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

D;.;.;D;.

Vest4

0.30

MutPred

0.62

Gain of disorder (P = 0.0339);.;.;Gain of disorder (P = 0.0339);.;

MVP

0.56

MPC

1.0

ClinPred

0.97

GERP RS

2.9

Varity_R

0.74

gMVP

0.26

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