Variant 1-247156840-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001297568.2(ZNF124):c.782C>G(p.Pro261Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF124
NM_001297568.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.12

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF124	NM_001297568.2 linkuse as main transcript	c.782C>G	p.Pro261Arg	missense_variant	4/4	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.782C>G	p.Pro261Arg	missense_variant	4/4	1	NM_001297568.2	ENSP00000440365	P1	Q15973-3
ZNF124	ENST00000340684.10 linkuse as main transcript	c.596C>G	p.Pro199Arg	missense_variant	4/4	1		ENSP00000340749		Q15973-4
ZNF124	ENST00000472531.5 linkuse as main transcript	c.218+2166C>G		intron_variant		2		ENSP00000462445		Q15973-5
ZNF124	ENST00000491356.5 linkuse as main transcript	c.218+2166C>G		intron_variant		2		ENSP00000463191

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151298

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

AF:

0.00000342

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

151298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73902

Gnomad4 AFR

AF:

0.00

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

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

May 11, 2022

The c.596C>G (p.P199R) alteration is located in exon 4 (coding exon 4) of the ZNF124 gene. This alteration results from a C to G substitution at nucleotide position 596, causing the proline (P) at amino acid position 199 to be replaced by an arginine (R). 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

0.24

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.0026

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

.;L

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-8.3

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

1.0

D;D

Vest4

0.33

MutPred

0.62

.;Gain of MoRF binding (P = 0.0343);

MVP

0.48

MPC

0.37

ClinPred

0.99

GERP RS

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.023

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.

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