9-101408158-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003452.4(ZNF189):​c.390C>G​(p.Phe130Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ZNF189
NM_003452.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.503
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.112724096).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF189NM_003452.4 linkc.390C>G p.Phe130Leu missense_variant Exon 3 of 3 ENST00000339664.7 NP_003443.2 O75820-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF189ENST00000339664.7 linkc.390C>G p.Phe130Leu missense_variant Exon 3 of 3 1 NM_003452.4 ENSP00000342019.2 O75820-1
ZNF189ENST00000374861.7 linkc.348C>G p.Phe116Leu missense_variant Exon 3 of 3 1 ENSP00000363995.3 O75820-2
ZNF189ENST00000259395.4 linkc.264C>G p.Phe88Leu missense_variant Exon 4 of 4 1 ENSP00000259395.4 O75820-4
ZNF189ENST00000615466.1 linkc.*211C>G 3_prime_UTR_variant Exon 4 of 4 3 ENSP00000483461.1 A0A087X0K2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
33
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.390C>G (p.F130L) alteration is located in exon 3 (coding exon 3) of the ZNF189 gene. This alteration results from a C to G substitution at nucleotide position 390, causing the phenylalanine (F) at amino acid position 130 to be replaced by a leucine (L). 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
Pathogenic
0.57
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
11
DANN
Benign
0.97
DEOGEN2
Benign
0.047
.;T;.
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.0091
N
LIST_S2
Benign
0.27
T;T;T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Pathogenic
3.1
.;M;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.14
T;T;T
Sift4G
Uncertain
0.037
D;D;D
Polyphen
0.0040
.;B;.
Vest4
0.15
MutPred
0.29
.;Gain of catalytic residue at F130 (P = 0.0178);.;
MVP
0.56
MPC
0.069
ClinPred
0.37
T
GERP RS
1.4
Varity_R
0.078
gMVP
0.13

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.

Other links and lift over

dbSNP: rs1830782098; hg19: chr9-104170440; API