dbSNP rs1208606: ZNF25:p.Asn453Lys (chr10-37952139-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_145011.4(ZNF25):c.1359T>G(p.Asn453Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,562,488 control chromosomes in the GnomAD database, including 4,950 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.060 ( 352 hom., cov: 33)

Exomes 𝑓: 0.076 ( 4598 hom. )

Consequence

ZNF25
NM_145011.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.142

Publications

23 publications found

Variant links:

Genes affected

ZNF25 (HGNC:13043): (zinc finger protein 25) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF25 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 (MetaRNN=0.0018883944).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF25	NM_145011.4 link	c.1359T>G	p.Asn453Lys	missense_variant	Exon 6 of 6	ENST00000302609.8	NP_659448.1	P17030-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF25	ENST00000302609.8 link	c.1359T>G	p.Asn453Lys	missense_variant	Exon 6 of 6	1	NM_145011.4	ENSP00000302222.7		P17030-1
ZNF25	ENST00000374633.5 link	n.1589T>G		non_coding_transcript_exon_variant	Exon 7 of 7	1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9127

AN:

152160

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.0645

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.0666

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.0717

GnomAD2 exomes

AF:

0.0600

AC:

12624

AN:

210314

AF XY:

0.0620

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.0492

Gnomad ASJ exome

AF:

0.0843

Gnomad EAS exome

AF:

0.0000593

Gnomad FIN exome

AF:

0.0716

Gnomad NFE exome

AF:

0.0861

Gnomad OTH exome

AF:

0.0742

GnomAD4 exome

AF:

0.0763

AC:

107644

AN:

1410210

Hom.:

4598

Cov.:

AF XY:

0.0748

AC XY:

52114

AN XY:

697124

show subpopulations

African (AFR)

AF:

0.0140

AC:

437

AN:

31248

American (AMR)

AF:

0.0515

AC:

1773

AN:

34414

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

1883

AN:

22820

East Asian (EAS)

AF:

0.0000510

AC:

AN:

39186

South Asian (SAS)

AF:

0.0126

AC:

985

AN:

78104

European-Finnish (FIN)

AF:

0.0709

AC:

3681

AN:

51892

Middle Eastern (MID)

AF:

0.0745

AC:

410

AN:

5500

European-Non Finnish (NFE)

AF:

0.0865

AC:

94224

AN:

1089030

Other (OTH)

AF:

0.0732

AC:

4249

AN:

58016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

4819

9637

14456

19274

24093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3400

6800

10200

13600

17000

<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:

0.0599

AC:

9129

AN:

152278

Hom.:

352

Cov.:

AF XY:

0.0570

AC XY:

4247

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0168

AC:

697

AN:

41566

American (AMR)

AF:

0.0644

AC:

986

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0847

AC:

294

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0666

AC:

706

AN:

10598

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0896

AC:

6096

AN:

68014

Other (OTH)

AF:

0.0710

AC:

150

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

444

888

1333

1777

2221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0793

Hom.:

1739

Bravo

AF:

0.0590

TwinsUK

AF:

0.0831

AC:

308

ALSPAC

AF:

0.0825

AC:

318

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.0880

AC:

757

ExAC

AF:

0.0567

AC:

6878

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.21

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.035

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.10

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.18

PhyloP100

-0.14

PrimateAI

Benign

0.35

PROVEAN

Benign

1.2

REVEL

Benign

0.072

Sift

Benign

0.15

Sift4G

Uncertain

0.044

Polyphen

0.0

Vest4

0.027

MutPred

0.24

Gain of methylation at N453 (P = 1e-04);

MPC

0.051

ClinPred

0.00058

GERP RS

-0.70

Varity_R

0.043

gMVP

0.018

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