Variant 19-44108078-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001321645.3(ZNF224):c.1918A>G(p.Lys640Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,613,870 control chromosomes in the GnomAD database, including 506,347 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 0.70 ( 38564 hom., cov: 32)

Exomes 𝑓: 0.79 ( 467783 hom. )

Consequence

ZNF224
NM_001321645.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.558

Variant links:

Genes affected

ZNF224 (HGNC:13017): (zinc finger protein 224) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein represses transcription of the aldolase A gene, which encodes a key enzyme in glycolysis. The encoded zinc-finger protein may also function as a transcriptional co-activator with Wilms' tumor protein 1 to regulate apoptotic genes in leukemia. [provided by RefSeq, Jul 2016]

ZNF224 links:

ZNF225-AS1 (HGNC:):

ZNF225-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5387097E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF224	NM_001321645.3 linkuse as main transcript	c.1918A>G	p.Lys640Glu	missense_variant	6/6	ENST00000693561.1	NP_001308574.1	Q9NZL3
ZNF224	NM_013398.5 linkuse as main transcript	c.1918A>G	p.Lys640Glu	missense_variant	6/6		NP_037530.2	Q9NZL3
ZNF225-AS1	NR_033341.1 linkuse as main transcript	n.622T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF224	ENST00000693561.1 linkuse as main transcript	c.1918A>G	p.Lys640Glu	missense_variant	6/6		NM_001321645.3	ENSP00000508532.1		Q9NZL3

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

105851

AN:

151880

Hom.:

38550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.722

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.782

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.829

Gnomad OTH

AF:

0.724

GnomAD3 exomes

AF:

0.710

AC:

178451

AN:

251408

Hom.:

65991

AF XY:

0.723

AC XY:

98217

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.511

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.771

Gnomad EAS exome

AF:

0.549

Gnomad SAS exome

AF:

0.685

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.824

Gnomad OTH exome

AF:

0.756

GnomAD4 exome

AF:

0.794

AC:

1160511

AN:

1461870

Hom.:

467783

Cov.:

AF XY:

0.793

AC XY:

576768

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.506

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.773

Gnomad4 EAS exome

AF:

0.545

Gnomad4 SAS exome

AF:

0.689

Gnomad4 FIN exome

AF:

0.770

Gnomad4 NFE exome

AF:

0.835

Gnomad4 OTH exome

AF:

0.765

GnomAD4 genome

AF:

0.697

AC:

105896

AN:

152000

Hom.:

38564

Cov.:

AF XY:

0.689

AC XY:

51159

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.782

Gnomad4 EAS

AF:

0.553

Gnomad4 SAS

AF:

0.683

Gnomad4 FIN

AF:

0.767

Gnomad4 NFE

AF:

0.829

Gnomad4 OTH

AF:

0.722

Alfa

AF:

0.796

Hom.:

94751

Bravo

AF:

0.673

TwinsUK

AF:

0.838

AC:

3108

ALSPAC

AF:

0.841

AC:

3242

ESP6500AA

AF:

0.509

AC:

2243

ESP6500EA

AF:

0.819

AC:

7041

ExAC

AF:

0.715

AC:

86831

Asia WGS

AF:

0.590

AC:

2056

AN:

3478

EpiCase

AF:

0.831

EpiControl

AF:

0.829

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.5

DANN

Benign

0.72

DEOGEN2

Benign

0.0077

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.085

MetaRNN

Benign

0.0000015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.12

REVEL

Benign

0.015

Sift

Benign

0.62

Sift4G

Benign

0.21

Polyphen

0.030

Vest4

0.020

MPC

0.13

ClinPred

0.0014

GERP RS

-4.3

Varity_R

0.044

gMVP

0.015

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