Variant 7-149104519-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000378061.7(ZNF425):c.1352T>G(p.Phe451Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000568 in 1,602,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

ZNF425
ENST00000378061.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Variant links:

Genes affected

ZNF425 (HGNC:20690): (zinc finger protein 425) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF425 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3961486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF425	NM_001001661.3 linkuse as main transcript	c.1352T>G	p.Phe451Cys	missense_variant	4/4	ENST00000378061.7	NP_001001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF425	ENST00000378061.7 linkuse as main transcript	c.1352T>G	p.Phe451Cys	missense_variant	4/4	1	NM_001001661.3	ENSP00000367300	P1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000458

AC:

AN:

240244

Hom.:

AF XY:

0.0000384

AC XY:

AN XY:

130060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000488

Gnomad NFE exome

AF:

0.0000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000586

AC:

AN:

1450958

Hom.:

Cov.:

AF XY:

0.0000568

AC XY:

AN XY:

721320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000383

Gnomad4 NFE exome

AF:

0.0000731

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000858

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000412

AC:

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

Oct 05, 2022

The c.1352T>G (p.F451C) alteration is located in exon 4 (coding exon 4) of the ZNF425 gene. This alteration results from a T to G substitution at nucleotide position 1352, causing the phenylalanine (F) at amino acid position 451 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

0.89

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.37

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.47

M_CAP

Benign

0.00091

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

0.79

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.0

REVEL

Benign

0.22

Sift

Benign

0.067

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.27

MVP

0.75

MPC

1.2

ClinPred

0.58

GERP RS

1.9

Varity_R

0.23

gMVP

0.28

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over