dbSNP rs769617389: ZNF524:p.Ala112Val (chr19-55602447-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153219.4(ZNF524):c.335C>T(p.Ala112Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 1,443,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000055 ( 0 hom. )

Consequence

ZNF524
NM_153219.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1295754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF524	NM_153219.4 link	c.335C>T	p.Ala112Val	missense_variant	Exon 2 of 2	ENST00000301073.4	NP_694951.1	Q96C55
ZNF524	XM_011526487.3 link	c.653C>T	p.Ala218Val	missense_variant	Exon 2 of 2		XP_011524789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF524	ENST00000301073.4 link	c.335C>T	p.Ala112Val	missense_variant	Exon 2 of 2	1	NM_153219.4	ENSP00000301073.2	Q96C55
ZNF524	ENST00000591046.1 link	c.335C>T	p.Ala112Val	missense_variant	Exon 1 of 1	6		ENSP00000466907.1	Q96C55
ZNF524	ENST00000589521.1 link	c.335C>T	p.Ala112Val	missense_variant	Exon 2 of 2	3		ENSP00000467175.1	K7EP10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000554

AC:

AN:

1443304

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

717378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33066

American (AMR)

AF:

0.00

AC:

AN:

43312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25838

East Asian (EAS)

AF:

0.00

AC:

AN:

38740

South Asian (SAS)

AF:

0.00

AC:

AN:

84350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00000723

AC:

AN:

1106802

Other (OTH)

AF:

0.00

AC:

AN:

59774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 15, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.335C>T (p.A112V) 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 335, causing the alanine (A) at amino acid position 112 to be replaced by a valine (V). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.56

T;.;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

.;L;L

PhyloP100

1.3

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.13

.;N;.

REVEL

Benign

0.074

Sift

Benign

0.11

.;T;.

Sift4G

Benign

0.065

T;T;T

Polyphen

0.96

.;D;D

Vest4

0.11, 0.099

MutPred

0.40

Loss of ubiquitination at K111 (P = 0.0421);Loss of ubiquitination at K111 (P = 0.0421);Loss of ubiquitination at K111 (P = 0.0421);

MVP

0.26

MPC

0.50

ClinPred

0.36

GERP RS

3.3

PromoterAI

-0.073

Neutral

(source)

Varity_R

0.050

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over