Genetic Variant NM_006961.4:c.671G>A (chr16-71475876-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

GnomAD2 exomes

AF:

0.0237

AC:

5938

AN:

250722

AF XY:

0.0233

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 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

African (AFR)

AF:

0.00436

AC:

146

AN:

33462

American (AMR)

AF:

0.0146

AC:

654

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

2017

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00427

AC:

368

AN:

86228

European-Finnish (FIN)

AF:

0.0349

AC:

1864

AN:

53402

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0307

AC:

34113

AN:

1111514

Other (OTH)

AF:

0.0277

AC:

1670

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2599

5197

7796

10394

12993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1290

2580

3870

5160

6450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0212

AC:

3218

AN:

151548

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

1538

AN XY:

74036

show subpopulations

African (AFR)

AF:

0.00566

AC:

234

AN:

41328

American (AMR)

AF:

0.0141

AC:

214

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.0736

AC:

255

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00230

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.0397

AC:

418

AN:

10528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0293

AC:

1986

AN:

67832

Other (OTH)

AF:

0.0256

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

168

336

504

672

840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0275

Hom.:

301

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

(source)

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

PhyloP100

-0.060

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over