Genetic Variant NM_003452.4:c.182A>G (chr9-101407950-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003452.4(ZNF189):c.182A>G(p.Asp61Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,583,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF189
NM_003452.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Publications

0 publications found

Variant links:

Genes affected

ZNF189 (HGNC:12980): (zinc finger protein 189) Kruppel-like zinc finger proteins such as ZNF189 contain a conserved stretch of 7 amino acids that connects a variable number of DNA-binding zinc finger repeats of the cys(2)his(2) (C2H2) type (summarized by Odeberg et al., 1998 [PubMed 9653648]). Approximately 30% of human Kruppel-like zinc finger proteins contain an N-terminal Kruppel-associated box (KRAB) domain. The KRAB domain consists of approximately 75 amino acids that may be subdivided into an A box, which is present in every KRAB domain and is essential for transcriptional repression, and a B box, which is not always present.[supplied by OMIM, May 2010]

ZNF189 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06844029).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003452.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF189	NM_003452.4	MANE Select	c.182A>G	p.Asp61Gly	missense	Exon 3 of 3	NP_003443.2
ZNF189	NM_001278231.2		c.140A>G	p.Asp47Gly	missense	Exon 3 of 3	NP_001265160.1	O75820-2
ZNF189	NM_001278232.2		c.137A>G	p.Asp46Gly	missense	Exon 3 of 3	NP_001265161.1	B7ZLK9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF189	ENST00000339664.7	TSL:1 MANE Select	c.182A>G	p.Asp61Gly	missense	Exon 3 of 3	ENSP00000342019.2	O75820-1
ZNF189	ENST00000374861.7	TSL:1	c.140A>G	p.Asp47Gly	missense	Exon 3 of 3	ENSP00000363995.3	O75820-2
ZNF189	ENST00000259395.4	TSL:1	c.56A>G	p.Asp19Gly	missense	Exon 4 of 4	ENSP00000259395.4	O75820-4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000456

AC:

AN:

219256

AF XY:

0.0000254

show subpopulations

Gnomad AFR exome

AF:

0.0000657

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.000114

AC:

163

AN:

1431416

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

710564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31808

American (AMR)

AF:

0.00

AC:

AN:

39192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24254

East Asian (EAS)

AF:

0.00

AC:

AN:

39184

South Asian (SAS)

AF:

0.00

AC:

AN:

80178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.000145

AC:

159

AN:

1099868

Other (OTH)

AF:

0.0000678

AC:

AN:

58992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.037

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.12

M_CAP

Benign

0.0063

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

3.7

PrimateAI

Benign

0.37

PROVEAN

Benign

1.6

REVEL

Benign

0.090

Sift

Benign

0.62

Sift4G

Benign

0.86

Polyphen

0.080

Vest4

0.14

MVP

0.46

MPC

0.077

ClinPred

0.062

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.28

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over