Genetic Variant ZNF583:c.233-149A>G (chr19-56422742-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_152478.3(ZNF583):c.233-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 525,936 control chromosomes in the GnomAD database, including 86,601 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 0.57 ( 24850 hom., cov: 32)

Exomes 𝑓: 0.56 ( 61751 hom. )

Consequence

ZNF583
NM_152478.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.83

Publications

6 publications found

Variant links:

Genes affected

ZNF583 (HGNC:26427): (zinc finger protein 583) 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 regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF583 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF583	NM_152478.3 link	c.233-149A>G		intron_variant	Intron 4 of 4	ENST00000333201.13	NP_689691.2	Q96ND8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF583	ENST00000333201.13 link	c.233-149A>G	intron_variant	Intron 4 of 4	2	NM_152478.3	ENSP00000388502.2	Q96ND8
ZNF583	ENST00000291598.11 link	c.233-149A>G	intron_variant	Intron 4 of 4	3		ENSP00000291598.7	Q96ND8
ZNF583	ENST00000391778.3 link	c.233-149A>G	intron_variant	Intron 4 of 4	4		ENSP00000375657.3	I3L0C4
ZNF583	ENST00000537943.5 link	c.233-149A>G	intron_variant	Intron 4 of 4	3		ENSP00000444291.1	F5GZQ5

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86110

AN:

151862

Hom.:

24801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.609

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.536

GnomAD4 exome

AF:

0.564

AC:

211005

AN:

373956

Hom.:

61751

AF XY:

0.565

AC XY:

109499

AN XY:

193970

show subpopulations

African (AFR)

AF:

0.597

AC:

5339

AN:

8944

American (AMR)

AF:

0.625

AC:

6850

AN:

10966

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

4956

AN:

11092

East Asian (EAS)

AF:

0.882

AC:

22258

AN:

25222

South Asian (SAS)

AF:

0.619

AC:

15075

AN:

24358

European-Finnish (FIN)

AF:

0.623

AC:

14815

AN:

23762

Middle Eastern (MID)

AF:

0.458

AC:

737

AN:

1608

European-Non Finnish (NFE)

AF:

0.524

AC:

129024

AN:

246396

Other (OTH)

AF:

0.553

AC:

11951

AN:

21608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

4160

8319

12479

16638

20798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1294

2588

3882

5176

6470

<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:

0.567

AC:

86217

AN:

151980

Hom.:

24850

Cov.:

AF XY:

0.572

AC XY:

42494

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.587

AC:

24319

AN:

41434

American (AMR)

AF:

0.606

AC:

9258

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1484

AN:

3466

East Asian (EAS)

AF:

0.879

AC:

4562

AN:

5188

South Asian (SAS)

AF:

0.624

AC:

3008

AN:

4818

European-Finnish (FIN)

AF:

0.609

AC:

6430

AN:

10554

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35277

AN:

67928

Other (OTH)

AF:

0.539

AC:

1136

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1841

3682

5523

7364

9205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.548

Hom.:

3178

Bravo

AF:

0.567

Asia WGS

AF:

0.739

AC:

2551

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.065

(source)

DANN

Benign

0.68

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over