Variant 10-37952139-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

ZNF25 (HGNC:):

ZNF25 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZNF25	NM_145011.4 linkuse as main transcript	c.1359T>G	p.Asn453Lys	missense_variant	6/6	ENST00000302609.8	NP_659448.1	P17030-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF25	ENST00000302609.8 linkuse as main transcript	c.1359T>G	p.Asn453Lys	missense_variant	6/6	1	NM_145011.4	ENSP00000302222.7		P17030-1
ZNF25	ENST00000374633.5 linkuse as main transcript	n.1589T>G		non_coding_transcript_exon_variant	7/7	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

GnomAD3 exomes

AF:

0.0600

AC:

12624

AN:

210314

Hom.:

522

AF XY:

0.0620

AC XY:

7038

AN XY:

113454

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 SAS exome

AF:

0.0124

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

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.0515

Gnomad4 ASJ exome

AF:

0.0825

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.0126

Gnomad4 FIN exome

AF:

0.0709

Gnomad4 NFE exome

AF:

0.0865

Gnomad4 OTH exome

AF:

0.0732

GnomAD4 genome

AF:

0.0599

AC:

9129

AN:

152278

Hom.:

352

Cov.:

AF XY:

0.0570

AC XY:

4247

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.0644

Gnomad4 ASJ

AF:

0.0847

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.0666

Gnomad4 NFE

AF:

0.0896

Gnomad4 OTH

AF:

0.0710

Alfa

AF:

0.0838

Hom.:

1337

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

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over