Variant 19-55602294-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153219.4(ZNF524):c.182G>A(p.Gly61Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,254 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ZNF524
NM_153219.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.295

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051265687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF524	NM_153219.4 linkuse as main transcript	c.182G>A	p.Gly61Glu	missense_variant	2/2	ENST00000301073.4	NP_694951.1	Q96C55
ZNF524	XM_011526487.3 linkuse as main transcript	c.500G>A	p.Gly167Glu	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.182G>A	p.Gly61Glu	missense_variant	2/2	1	NM_153219.4	ENSP00000301073.2	Q96C55
ZNF524	ENST00000591046.1 linkuse as main transcript	c.182G>A	p.Gly61Glu	missense_variant	1/1	6		ENSP00000466907.1	Q96C55
ZNF524	ENST00000589521.1 linkuse as main transcript	c.182G>A	p.Gly61Glu	missense_variant	2/2	3		ENSP00000467175.1	K7EP10

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Sep 17, 2021

The c.182G>A (p.G61E) alteration is located in exon 2 (coding exon 1) of the ZNF524 gene. This alteration results from a G to A substitution at nucleotide position 182, causing the glycine (G) at amino acid position 61 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

0.21

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.055

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.45

T;.;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

.;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.5

.;N;.

REVEL

Benign

0.025

Sift

Benign

0.47

.;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.068, 0.062

MutPred

0.43

Loss of MoRF binding (P = 0.0555);Loss of MoRF binding (P = 0.0555);Loss of MoRF binding (P = 0.0555);

MVP

0.11

MPC

0.52

ClinPred

0.026

GERP RS

-1.5

Varity_R

0.046

gMVP

0.14

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