Variant 19-55602362-C-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_153219.4(ZNF524):c.250C>T(p.Leu84Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000769 in 1,561,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

ZNF524
NM_153219.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

Variant links:

Genes affected

ZNF524 (HGNC:28322): (zinc finger protein 524) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF524 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=0.13476771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF524	NM_153219.4 linkuse as main transcript	c.250C>T	p.Leu84Phe	missense_variant	2/2	ENST00000301073.4	NP_694951.1	Q96C55
ZNF524	XM_011526487.3 linkuse as main transcript	c.568C>T	p.Leu190Phe	missense_variant	2/2		XP_011524789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF524	ENST00000301073.4 linkuse as main transcript	c.250C>T	p.Leu84Phe	missense_variant	2/2	1	NM_153219.4	ENSP00000301073.2	Q96C55
ZNF524	ENST00000591046.1 linkuse as main transcript	c.250C>T	p.Leu84Phe	missense_variant	1/1	6		ENSP00000466907.1	Q96C55
ZNF524	ENST00000589521.1 linkuse as main transcript	c.250C>T	p.Leu84Phe	missense_variant	2/2	3		ENSP00000467175.1	K7EP10

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

166492

Hom.:

AF XY:

0.0000112

AC XY:

AN XY:

89446

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000412

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000151

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000639

AC:

AN:

1408908

Hom.:

Cov.:

AF XY:

0.00000431

AC XY:

AN XY:

696618

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:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000737

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000848

AC:

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

Aug 20, 2024

The c.250C>T (p.L84F) alteration is located in exon 2 (coding exon 1) of the ZNF524 gene. This alteration results from a C to T substitution at nucleotide position 250, causing the leucine (L) at amino acid position 84 to be replaced by a phenylalanine (F). 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

0.29

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.026

T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.57

T;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

.;L;L

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.25

.;N;.

REVEL

Benign

0.052

Sift

Benign

0.63

.;T;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.82

.;P;P

Vest4

0.27, 0.25

MutPred

0.46

Gain of catalytic residue at L84 (P = 0.1256);Gain of catalytic residue at L84 (P = 0.1256);Gain of catalytic residue at L84 (P = 0.1256);

MVP

0.28

MPC

0.57

ClinPred

0.17

GERP RS

2.0

Varity_R

0.061

gMVP

0.20

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