Genetic Variant ZNF583:p.Ala500Ala (chr19-56424158-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_152478.3(ZNF583):c.1500A>G(p.Ala500Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,613,570 control chromosomes in the GnomAD database, including 241,419 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 0.56 ( 24461 hom., cov: 32)

Exomes 𝑓: 0.54 ( 216958 hom. )

Consequence

ZNF583
NM_152478.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.22

Publications

18 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=-2.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF583	NM_152478.3 link	c.1500A>G	p.Ala500Ala	synonymous_variant	Exon 5 of 5	ENST00000333201.13	NP_689691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ZNF583	ENST00000333201.13 link	c.1500A>G	p.Ala500Ala	synonymous_variant	Exon 5 of 5	2	NM_152478.3	ENSP00000388502.2
ZNF583	ENST00000585612.1 link	n.653+356A>G		intron_variant	Intron 1 of 1	1
ZNF583	ENST00000291598.11 link	c.1500A>G	p.Ala500Ala	synonymous_variant	Exon 5 of 5	3		ENSP00000291598.7

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85454

AN:

151888

Hom.:

24419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.532

GnomAD2 exomes

AF:

0.577

AC:

144701

AN:

250734

AF XY:

0.569

show subpopulations

Gnomad AFR exome

AF:

0.569

Gnomad AMR exome

AF:

0.646

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.879

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.540

AC:

789042

AN:

1461564

Hom.:

216958

Cov.:

AF XY:

0.540

AC XY:

392639

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.567

AC:

18987

AN:

33474

American (AMR)

AF:

0.642

AC:

28730

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

11381

AN:

26126

East Asian (EAS)

AF:

0.878

AC:

34857

AN:

39684

South Asian (SAS)

AF:

0.595

AC:

51361

AN:

86252

European-Finnish (FIN)

AF:

0.610

AC:

32464

AN:

53256

Middle Eastern (MID)

AF:

0.416

AC:

2398

AN:

5766

European-Non Finnish (NFE)

AF:

0.518

AC:

576149

AN:

1111896

Other (OTH)

AF:

0.542

AC:

32715

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21083

42166

63248

84331

105414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16768

33536

50304

67072

83840

<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:

0.563

AC:

85552

AN:

152006

Hom.:

24461

Cov.:

AF XY:

0.568

AC XY:

42161

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.572

AC:

23714

AN:

41466

American (AMR)

AF:

0.604

AC:

9238

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1482

AN:

3464

East Asian (EAS)

AF:

0.879

AC:

4545

AN:

5172

South Asian (SAS)

AF:

0.625

AC:

3008

AN:

4814

European-Finnish (FIN)

AF:

0.607

AC:

6416

AN:

10566

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.519

AC:

35280

AN:

67928

Other (OTH)

AF:

0.535

AC:

1128

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1908

3816

5725

7633

9541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.524

Hom.:

61962

Bravo

AF:

0.562

Asia WGS

AF:

0.738

AC:

2562

AN:

3478

EpiCase

AF:

0.505

EpiControl

AF:

0.494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.9

(source)

DANN

Benign

0.79

PhyloP100

-2.2

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