Variant 9-101408199-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000339664.7(ZNF189):c.431A>G(p.Glu144Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF189
ENST00000339664.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.739

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:

ZNF189 (HGNC:):

ZNF189 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03190431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF189	NM_003452.4 linkuse as main transcript	c.431A>G	p.Glu144Gly	missense_variant	3/3	ENST00000339664.7	NP_003443.2	O75820-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF189	ENST00000339664.7 linkuse as main transcript	c.431A>G	p.Glu144Gly	missense_variant	3/3	1	NM_003452.4	ENSP00000342019.2	O75820-1
ZNF189	ENST00000374861.7 linkuse as main transcript	c.389A>G	p.Glu130Gly	missense_variant	3/3	1		ENSP00000363995.3	O75820-2
ZNF189	ENST00000259395.4 linkuse as main transcript	c.305A>G	p.Glu102Gly	missense_variant	4/4	1		ENSP00000259395.4	O75820-4
ZNF189	ENST00000615466.1 linkuse as main transcript	c.*252A>G		3_prime_UTR_variant	4/4	3		ENSP00000483461.1	A0A087X0K2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.431A>G (p.E144G) alteration is located in exon 3 (coding exon 3) of the ZNF189 gene. This alteration results from a A to G substitution at nucleotide position 431, causing the glutamic acid (E) at amino acid position 144 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.24

DEOGEN2

Benign

0.0050

.;T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.029

T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

.;N;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

3.4

N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0020

.;B;.

Vest4

0.20

MutPred

0.29

.;Loss of ubiquitination at K149 (P = 0.0219);.;

MVP

0.15

MPC

0.18

ClinPred

0.14

GERP RS

4.7

Varity_R

0.053

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over