Variant 19-55602182-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_153219.4(ZNF524):c.70T>C(p.Ser24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000808 in 1,608,302 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

ZNF524
NM_153219.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.848

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005889386).

BP6

Variant 19-55602182-T-C is Benign according to our data. Variant chr19-55602182-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3196456.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF524	NM_153219.4 linkuse as main transcript	c.70T>C	p.Ser24Pro	missense_variant	2/2	ENST00000301073.4	NP_694951.1	Q96C55
ZNF524	XM_011526487.3 linkuse as main transcript	c.388T>C	p.Ser130Pro	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.70T>C	p.Ser24Pro	missense_variant	2/2	1	NM_153219.4	ENSP00000301073.2	Q96C55
ZNF524	ENST00000591046.1 linkuse as main transcript	c.70T>C	p.Ser24Pro	missense_variant	1/1	6		ENSP00000466907.1	Q96C55
ZNF524	ENST00000589521.1 linkuse as main transcript	c.70T>C	p.Ser24Pro	missense_variant	2/2	3		ENSP00000467175.1	K7EP10

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000143

AC:

AN:

245094

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

133072

show subpopulations

Gnomad AFR exome

AF:

0.00157

Gnomad AMR exome

AF:

0.000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000495

AC:

AN:

1456008

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

724128

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.000295

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:

0.00

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000381

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000721

Hom.:

Bravo

AF:

0.000510

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0019

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.00087

LIST_S2

Benign

0.20

T;.;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

.;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.1

.;N;.

REVEL

Benign

0.014

Sift

Benign

0.27

.;T;.

Sift4G

Benign

0.83

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.081, 0.076

MVP

0.14

MPC

0.50

ClinPred

0.0036

GERP RS

1.6

Varity_R

0.079

gMVP

0.068

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