chr7-99486722-A-T

Variant summary

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

The NM_213603.3(ZNF789):​c.512A>T​(p.Lys171Met) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF789
NM_213603.3 missense

Scores

3
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.347
Variant links:
Genes affected
ZNF789 (HGNC:27801): (zinc finger protein 789) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
ZNF394 (HGNC:18832): (zinc finger protein 394) The protein encoded by this gene is a zinc finger protein that inhibits the transcription of mitogen-activated protein kinase signaling pathways. The encoded protein may be involved in cardiac function. [provided by RefSeq, Sep 2016]

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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=0.23495719).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF789NM_213603.3 linkc.512A>T p.Lys171Met missense_variant Exon 5 of 5 ENST00000331410.10 NP_998768.2 Q5FWF6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF789ENST00000331410.10 linkc.512A>T p.Lys171Met missense_variant Exon 5 of 5 1 NM_213603.3 ENSP00000331927.5 Q5FWF6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.512A>T (p.K171M) alteration is located in exon 5 (coding exon 4) of the ZNF789 gene. This alteration results from a A to T substitution at nucleotide position 512, causing the lysine (K) at amino acid position 171 to be replaced by a methionine (M). 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
0.17
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Pathogenic
3.8
H
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.051
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.99
D
Vest4
0.35
MutPred
0.45
Loss of methylation at K171 (P = 0.0029);
MVP
0.40
MPC
0.82
ClinPred
0.96
D
GERP RS
0.018
Varity_R
0.26
gMVP
0.065

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.

Other links and lift over

hg19: chr7-99084345; API