Variant chr10-37957057-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000302609.8(ZNF25):c.201G>T(p.Trp67Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF25
ENST00000302609.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF25	NM_145011.4 linkuse as main transcript	c.201G>T	p.Trp67Cys	missense_variant	4/6	ENST00000302609.8	NP_659448.1	P17030-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF25	ENST00000302609.8 linkuse as main transcript	c.201G>T	p.Trp67Cys	missense_variant	4/6	1	NM_145011.4	ENSP00000302222.7	P17030-1
ZNF25	ENST00000374633.5 linkuse as main transcript	n.431G>T		non_coding_transcript_exon_variant	5/7	1
ZNF25	ENST00000467975.2 linkuse as main transcript	n.373G>T		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2024

The c.201G>T (p.W67C) alteration is located in exon 4 (coding exon 3) of the ZNF25 gene. This alteration results from a G to T substitution at nucleotide position 201, causing the tryptophan (W) at amino acid position 67 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.29

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-9.8

REVEL

Benign

0.28

Sift

Benign

0.072

Sift4G

Uncertain

0.027

Polyphen

1.0

Vest4

0.73

MutPred

0.48

Gain of catalytic residue at P66 (P = 0.0137);

MVP

0.60

MPC

0.38

ClinPred

1.0

GERP RS

4.9

Varity_R

0.32

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over