Genetic Variant ENST00000444991.6:c.1462T>G (chr19-36997153-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000444991.6(ZNF568):c.1462T>G(p.Tyr488Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,586,450 control chromosomes in the GnomAD database, including 22,265 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2431 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19834 hom. )

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.62

Publications

16 publications found

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:

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new If you want to explore the variant's impact on the transcript ENST00000444991.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061773956).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444991.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF568	NM_001204838.2		c.1462T>G	p.Tyr488Asp	missense	Exon 10 of 10	NP_001191767.1	C9JLX5
	ZNF568	NM_001204839.2		c.1270T>G	p.Tyr424Asp	missense	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF568	ENST00000444991.6	TSL:1	c.1462T>G	p.Tyr488Asp	missense	Exon 10 of 10	ENSP00000389794.2	C9JLX5
ENSG00000291239	ENST00000706165.1		c.1462T>G	p.Tyr488Asp	missense	Exon 12 of 12	ENSP00000516244.1	C9JLX5
ZNF568	ENST00000591887.1	TSL:1	n.1631T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26840

AN:

151810

Hom.:

2425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.189

GnomAD2 exomes

AF:

0.172

AC:

36021

AN:

209504

AF XY:

0.176

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.164

AC:

234813

AN:

1434522

Hom.:

19834

Cov.:

AF XY:

0.166

AC XY:

118069

AN XY:

712058

show subpopulations

African (AFR)

AF:

0.209

AC:

6860

AN:

32772

American (AMR)

AF:

0.144

AC:

5856

AN:

40598

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4487

AN:

25748

East Asian (EAS)

AF:

0.185

AC:

7090

AN:

38396

South Asian (SAS)

AF:

0.241

AC:

20082

AN:

83432

European-Finnish (FIN)

AF:

0.165

AC:

7827

AN:

47384

Middle Eastern (MID)

AF:

0.221

AC:

1268

AN:

5750

European-Non Finnish (NFE)

AF:

0.156

AC:

171305

AN:

1100774

Other (OTH)

AF:

0.168

AC:

10038

AN:

59668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

11843

23687

35530

47374

59217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6302

12604

18906

25208

31510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.177

AC:

26865

AN:

151928

Hom.:

2431

Cov.:

AF XY:

0.178

AC XY:

13232

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.206

AC:

8537

AN:

41426

American (AMR)

AF:

0.171

AC:

2607

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

620

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

869

AN:

5146

South Asian (SAS)

AF:

0.261

AC:

1253

AN:

4796

European-Finnish (FIN)

AF:

0.172

AC:

1820

AN:

10558

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10559

AN:

67954

Other (OTH)

AF:

0.188

AC:

396

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1103

2206

3309

4412

5515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.159

Hom.:

3659

Bravo

AF:

0.175

Asia WGS

AF:

0.221

AC:

768

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.1

PhyloP100

7.6

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over