Genetic Variant ZNF19:p.Arg224Gln (chr16-71475876-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006961.4(ZNF19):c.671G>A(p.Arg224Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,612,794 control chromosomes in the GnomAD database, including 784 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.021 ( 51 hom., cov: 32)

Exomes 𝑓: 0.028 ( 733 hom. )

Consequence

ZNF19
NM_006961.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0600

Variant links:

Genes affected

ZNF19 (HGNC:12981): (zinc finger protein 19) The protein encoded by this gene contains a zinc finger, a nucleic acid-binding domain present in many transcription factors. This gene is located in a region next to ZNF23, a gene also encoding a zinc finger protein, on chromosome 16. [provided by RefSeq, Jul 2008]

ZNF19 links:

ENSG00000261611 (HGNC:):

ENSG00000261611 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020115674).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3218/151548) while in subpopulation NFE AF= 0.0293 (1986/67832). AF 95% confidence interval is 0.0282. There are 51 homozygotes in gnomad4. There are 1538 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF19	NM_006961.4 link	c.671G>A	p.Arg224Gln	missense_variant	Exon 6 of 6	ENST00000288177.10	NP_008892.2	P17023-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF19	ENST00000288177.10 link	c.671G>A	p.Arg224Gln	missense_variant	Exon 6 of 6	1	NM_006961.4	ENSP00000288177.5		P17023-1
ENSG00000261611	ENST00000561908.1 link	n.274+2352G>A		intron_variant	Intron 5 of 11	2		ENSP00000463741.1		J3QLW9

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3219

AN:

151426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00568

Gnomad AMI

AF:

0.0505

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.0736

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00230

Gnomad FIN

AF:

0.0397

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.0293

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0237

AC:

5938

AN:

250722

Hom.:

116

AF XY:

0.0233

AC XY:

3159

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.00493

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.0745

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00356

Gnomad FIN exome

AF:

0.0360

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0280

AC:

40861

AN:

1461246

Hom.:

733

Cov.:

AF XY:

0.0273

AC XY:

19840

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00436

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.0772

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00427

Gnomad4 FIN exome

AF:

0.0349

Gnomad4 NFE exome

AF:

0.0307

Gnomad4 OTH exome

AF:

0.0277

GnomAD4 genome

AF:

0.0212

AC:

3218

AN:

151548

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

1538

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.00566

Gnomad4 AMR

AF:

0.0141

Gnomad4 ASJ

AF:

0.0736

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00230

Gnomad4 FIN

AF:

0.0397

Gnomad4 NFE

AF:

0.0293

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0286

Hom.:

172

Bravo

AF:

0.0199

TwinsUK

AF:

0.0348

AC:

129

ALSPAC

AF:

0.0368

AC:

142

ESP6500AA

AF:

0.00614

AC:

ESP6500EA

AF:

0.0316

AC:

272

ExAC

AF:

0.0238

AC:

2890

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0266

EpiControl

AF:

0.0271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

T;.;.;T

Eigen

Benign

0.044

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.13

.;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.;.;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

N;N;.;N

REVEL

Benign

0.096

Sift

Benign

0.052

T;D;.;T

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.058

MPC

0.24

ClinPred

0.036

GERP RS

1.4

Varity_R

0.15

gMVP

0.058

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