Variant chr19-36546939-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000591340.6(ZNF529):c.1619G>C(p.Gly540Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF529
ENST00000591340.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.300

Variant links:

Genes affected

ZNF529 (HGNC:29328): (zinc finger protein 529) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF529 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=0.18386427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF529	NM_020951.5 linkuse as main transcript	c.1619G>C	p.Gly540Ala	missense_variant	5/5	ENST00000591340.6	NP_066002.3	Q6P280

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF529	ENST00000591340.6 linkuse as main transcript	c.1619G>C	p.Gly540Ala	missense_variant	5/5	1	NM_020951.5	ENSP00000465578.1	Q6P280
ZNF529	ENST00000334116.7 linkuse as main transcript	c.1304G>C	p.Gly435Ala	missense_variant	6/6	2		ENSP00000334695.7	A0A0C4DFR4
ZNF529	ENST00000452073.2 linkuse as main transcript	c.205+619G>C		intron_variant		3		ENSP00000465917.1	K7EL49
ZNF529	ENST00000590656.1 linkuse as main transcript	c.139+451G>C		intron_variant		3		ENSP00000468594.1	K7ES80

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249862

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

6.84e-7

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 15, 2022

The c.1619G>C (p.G540A) alteration is located in exon 6 (coding exon 4) of the ZNF529 gene. This alteration results from a G to C substitution at nucleotide position 1619, causing the glycine (G) at amino acid position 540 to be replaced by an alanine (A). 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

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.057

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

0.90

N;N

PrimateAI

Benign

0.22

REVEL

Benign

0.090

Sift4G

Uncertain

0.0080

D;D

Vest4

0.24

MVP

0.69

MPC

0.20

ClinPred

0.47

GERP RS

2.5

Varity_R

0.23

gMVP

0.039

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