Variant chr19-44106801-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001321645.3(ZNF224):c.641G>A(p.Ser214Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,613,906 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 22 hom. )

Consequence

ZNF224
NM_001321645.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.477

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:55916): (ZNF225 and ZNF224 antisense RNA 1)

ZNF225-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00393489).

BP6

Variant 19-44106801-G-A is Benign according to our data. Variant chr19-44106801-G-A is described in ClinVar as [Benign]. Clinvar id is 788470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0064 (975/152326) while in subpopulation AFR AF= 0.0226 (938/41574). AF 95% confidence interval is 0.0214. There are 9 homozygotes in gnomad4. There are 433 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF224	NM_001321645.3 linkuse as main transcript	c.641G>A	p.Ser214Asn	missense_variant	6/6	ENST00000693561.1	NP_001308574.1
ZNF225-AS1	NR_033341.1 linkuse as main transcript	n.1899C>T		non_coding_transcript_exon_variant	2/2
ZNF224	NM_013398.5 linkuse as main transcript	c.641G>A	p.Ser214Asn	missense_variant	6/6		NP_037530.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF224	ENST00000693561.1 linkuse as main transcript	c.641G>A	p.Ser214Asn	missense_variant	6/6		NM_001321645.3	ENSP00000508532	P1
ZNF225-AS1	ENST00000661725.1 linkuse as main transcript	n.1899C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00635

AC:

967

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00150

AC:

377

AN:

251080

Hom.:

AF XY:

0.000988

AC XY:

134

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0201

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000701

AC:

1024

AN:

1461580

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

422

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00640

AC:

975

AN:

152326

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

433

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00317

Hom.:

Bravo

AF:

0.00702

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00197

AC:

239

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0075

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.025

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.28

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.075

Sift

Benign

0.17

Sift4G

Benign

0.22

Polyphen

0.0020

Vest4

0.064

MVP

0.11

MPC

0.081

ClinPred

0.0011

GERP RS

2.0

Varity_R

0.040

gMVP

0.0055

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