Variant 19-55602186-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.74C>T(p.Pro25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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

ZNF524
NM_153219.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

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:

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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=0.09924263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF524	NM_153219.4 linkuse as main transcript	c.74C>T	p.Pro25Leu	missense_variant	2/2	ENST00000301073.4	NP_694951.1	Q96C55
ZNF524	XM_011526487.3 linkuse as main transcript	c.392C>T	p.Pro131Leu	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.74C>T	p.Pro25Leu	missense_variant	2/2	1	NM_153219.4	ENSP00000301073.2	Q96C55
ZNF524	ENST00000591046.1 linkuse as main transcript	c.74C>T	p.Pro25Leu	missense_variant	1/1	6		ENSP00000466907.1	Q96C55
ZNF524	ENST00000589521.1 linkuse as main transcript	c.74C>T	p.Pro25Leu	missense_variant	2/2	3		ENSP00000467175.1	K7EP10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724928

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

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

Nov 13, 2023

The c.74C>T (p.P25L) 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 74, causing the proline (P) at amino acid position 25 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.081

T;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.64

T;.;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.099

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

.;L;L

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.1

.;N;.

REVEL

Benign

0.024

Sift

Uncertain

0.0050

.;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0

.;B;B

Vest4

0.12, 0.11

MutPred

0.21

Loss of glycosylation at P25 (P = 0.0527);Loss of glycosylation at P25 (P = 0.0527);Loss of glycosylation at P25 (P = 0.0527);

MVP

0.19

MPC

0.40

ClinPred

0.28

GERP RS

2.4

Varity_R

0.12

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over