dbSNP rs12236219: ZNF169:p.Arg381Cys (chr9-94300699-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_194320.4(ZNF169):c.1141C>T(p.Arg381Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 1,613,872 control chromosomes in the GnomAD database, including 7,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.084 ( 994 hom., cov: 33)

Exomes 𝑓: 0.066 ( 6723 hom. )

Consequence

ZNF169
NM_194320.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Publications

29 publications found

Variant links:

Genes affected

ZNF169 (HGNC:12957): (zinc finger protein 169) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF169 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=0.005741477).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF169	NM_194320.4 link	c.1141C>T	p.Arg381Cys	missense_variant	Exon 5 of 5	ENST00000395395.7	NP_919301.2	Q14929

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF169	ENST00000395395.7 link	c.1141C>T	p.Arg381Cys	missense_variant	Exon 5 of 5	2	NM_194320.4	ENSP00000378792.2	Q14929
ZNF169	ENST00000718459.1 link	c.1144C>T	p.Arg382Cys	missense_variant	Exon 5 of 5			ENSP00000520837.1
ZNF169	ENST00000340911.8 link	c.*1130C>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000340711.4	Q5SR55

Frequencies

GnomAD3 genomes

AF:

0.0835

AC:

12694

AN:

151944

Hom.:

995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0810

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0914

GnomAD2 exomes

AF:

0.118

AC:

29740

AN:

251036

AF XY:

0.110

show subpopulations

Gnomad AFR exome

AF:

0.0811

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.0604

Gnomad EAS exome

AF:

0.377

Gnomad FIN exome

AF:

0.0436

Gnomad NFE exome

AF:

0.0447

Gnomad OTH exome

AF:

0.0839

GnomAD4 exome

AF:

0.0662

AC:

96844

AN:

1461808

Hom.:

6723

Cov.:

AF XY:

0.0671

AC XY:

48829

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0790

AC:

2645

AN:

33478

American (AMR)

AF:

0.285

AC:

12753

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0619

AC:

1619

AN:

26134

East Asian (EAS)

AF:

0.337

AC:

13377

AN:

39692

South Asian (SAS)

AF:

0.132

AC:

11403

AN:

86252

European-Finnish (FIN)

AF:

0.0440

AC:

2350

AN:

53418

Middle Eastern (MID)

AF:

0.0570

AC:

329

AN:

5768

European-Non Finnish (NFE)

AF:

0.0426

AC:

47421

AN:

1111990

Other (OTH)

AF:

0.0819

AC:

4947

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

6199

12398

18597

24796

30995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2164

4328

6492

8656

10820

<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:

0.0836

AC:

12706

AN:

152064

Hom.:

994

Cov.:

AF XY:

0.0883

AC XY:

6564

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0809

AC:

3357

AN:

41480

American (AMR)

AF:

0.194

AC:

2963

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0550

AC:

191

AN:

3470

East Asian (EAS)

AF:

0.355

AC:

1816

AN:

5122

South Asian (SAS)

AF:

0.153

AC:

738

AN:

4810

European-Finnish (FIN)

AF:

0.0387

AC:

410

AN:

10604

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0445

AC:

3023

AN:

67986

Other (OTH)

AF:

0.0927

AC:

196

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

521

1042

1564

2085

2606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0637

Hom.:

2633

Bravo

AF:

0.0974

TwinsUK

AF:

0.0372

AC:

138

ALSPAC

AF:

0.0423

AC:

163

ESP6500AA

AF:

0.0788

AC:

347

ESP6500EA

AF:

0.0442

AC:

380

ExAC

AF:

0.109

AC:

13268

Asia WGS

AF:

0.250

AC:

866

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0057

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

PhyloP100

1.3

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.056

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.14

MPC

0.38

ClinPred

0.056

GERP RS

0.85

Varity_R

0.33

gMVP

0.16

Mutation Taster

=98/2

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