Variant 1-247159050-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001297568.2(ZNF124):c.174C>A(p.Asp58Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF124
NM_001297568.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.781

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]

ZNF124 links:

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=0.13999462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF124	NM_001297568.2 linkuse as main transcript	c.174C>A	p.Asp58Glu	missense_variant	3/4	ENST00000543802.3	NP_001284497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF124	ENST00000543802.3 linkuse as main transcript	c.174C>A	p.Asp58Glu	missense_variant	3/4	1	NM_001297568.2	ENSP00000440365	P1	Q15973-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459826

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

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

Mar 24, 2023

The c.174C>A (p.D58E) alteration is located in exon 3 (coding exon 3) of the ZNF124 gene. This alteration results from a C to A substitution at nucleotide position 174, causing the aspartic acid (D) at amino acid position 58 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

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.0

DANN

Benign

0.62

DEOGEN2

Benign

0.045

.;T;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.022

T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.56

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.0

.;.;N;.

REVEL

Benign

0.046

Sift

Benign

0.32

.;.;T;.

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.97, 0.053

.;.;D;B

Vest4

0.16

MutPred

0.43

Gain of ubiquitination at K55 (P = 0.069);Gain of ubiquitination at K55 (P = 0.069);Gain of ubiquitination at K55 (P = 0.069);Gain of ubiquitination at K55 (P = 0.069);

MVP

0.43

MPC

0.35

ClinPred

0.17

GERP RS

0.43

Varity_R

0.094

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over