Variant 19-44131746-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000262894.11(ZNF225):c.1132G>A(p.Gly378Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000317 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

ZNF225
ENST00000262894.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

Variant links:

Genes affected

ZNF225 (HGNC:13018): (zinc finger protein 225) Predicted to enable DNA-binding transcription activator 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]

ZNF225 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23648801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF225	NM_013362.4 linkuse as main transcript	c.1132G>A	p.Gly378Arg	missense_variant	5/5	ENST00000262894.11	NP_037494.2	Q9UK10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF225	ENST00000262894.11 linkuse as main transcript	c.1132G>A	p.Gly378Arg	missense_variant	5/5	1	NM_013362.4	ENSP00000262894.5	Q9UK10
ZNF225	ENST00000590612.1 linkuse as main transcript	c.1132G>A	p.Gly378Arg	missense_variant	4/4	1		ENSP00000468686.1	Q9UK10
ZNF225	ENST00000592780.5 linkuse as main transcript	c.*913G>A		3_prime_UTR_variant	6/6	5		ENSP00000466889.1	K7ENC8

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152214

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000104

AC:

AN:

250314

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.0000642

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000334

AC:

489

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000340

AC XY:

247

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000427

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000145

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74356

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:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000413

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000584

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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 29, 2021

The c.1132G>A (p.G378R) alteration is located in exon 5 (coding exon 4) of the ZNF225 gene. This alteration results from a G to A substitution at nucleotide position 1132, causing the glycine (G) at amino acid position 378 to be replaced by an arginine (R). 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

Benign

0.34

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

T;T

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.12

.;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-6.2

D;.

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;D

Vest4

0.26

MutPred

0.76

Gain of MoRF binding (P = 0.0256);Gain of MoRF binding (P = 0.0256);

MVP

0.38

MPC

0.54

ClinPred

0.50

GERP RS

2.5

Varity_R

0.59

gMVP

0.027

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