NM_001297568.2:c.553A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001297568.2(ZNF124):​c.553A>G​(p.Lys185Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF124
NM_001297568.2 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05
Variant links:
Genes affected
ZNF124 (HGNC:12907): (zinc finger protein 124) This gene encodes a protein with an amino-terminal KRAB-A box and multiple repeated Kruppel-type (C2H2) zinc finger motifs at its carboxy terminus. The encoded protein may function as a transcription factor. Expression of this gene is increased after vascular endothelial growth factor (VEGF) stimulation in human leukemia cell lines and results in inhibition of apoptotic cell death induced by irradiation or exposure to etoposide. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34123284).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF124NM_001297568.2 linkc.553A>G p.Lys185Glu missense_variant Exon 4 of 4 ENST00000543802.3 NP_001284497.1 Q15973-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF124ENST00000543802.3 linkc.553A>G p.Lys185Glu missense_variant Exon 4 of 4 1 NM_001297568.2 ENSP00000440365.2 Q15973-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461866
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.367A>G (p.K123E) alteration is located in exon 4 (coding exon 4) of the ZNF124 gene. This alteration results from a A to G substitution at nucleotide position 367, causing the lysine (K) at amino acid position 123 to be replaced by a glutamic acid (E). 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
0.75
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
.;T
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.0052
N
LIST_S2
Uncertain
0.91
D;T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.34
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
.;M
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.11
Sift
Uncertain
0.022
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.20
MutPred
0.51
.;Loss of MoRF binding (P = 7e-04);
MVP
0.53
MPC
0.38
ClinPred
0.98
D
GERP RS
0.86
Varity_R
0.099
gMVP
0.014

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: rs1673185457; hg19: chr1-247320371; API