Variant chr19-9324741-C-T 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_001202406.1(ZNF559):c.97C>T(p.Pro33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000794 in 1,535,702 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

ZNF559
NM_001202406.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

ZNF559 (HGNC:28197): (zinc finger protein 559) 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]

ZNF559 links:

ZNF559-ZNF177 (HGNC:42964): (ZNF559-ZNF177 readthrough) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 559 (ZNF559) and zinc finger protein 177 (ZNF177) genes on chromosome 19. Alternative splicing results in multiple transcript variants, which encode the ZNF177 protein due to either leaky scanning by ribosomes, or absence of the ZNF559 start codon. [provided by RefSeq, Jan 2011]

ZNF559-ZNF177 links:

Genome browser will be placed here

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=0.0051368177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF559	NM_032497.3 link	c.-159C>T		5_prime_UTR_variant	2/7	ENST00000603380.6	NP_115886.1	Q9BR84-1A0A024R7B5B4DP29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF559	ENST00000603380 link	c.-159C>T		5_prime_UTR_variant	2/7	2	NM_032497.3	ENSP00000474760.1		Q9BR84-1
ZNF559-ZNF177	ENST00000541595 link	c.-519C>T		5_prime_UTR_variant	2/12	2		ENSP00000445323.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00174

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

GnomAD3 exomes

AF:

0.000267

AC:

AN:

134662

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

73322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00304

Gnomad SAS exome

AF:

0.0000889

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000482

GnomAD4 exome

AF:

0.0000817

AC:

113

AN:

1383770

Hom.:

Cov.:

AF XY:

0.0000747

AC XY:

AN XY:

682828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00260

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000107

AC:

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 28, 2023

The c.97C>T (p.P33S) alteration is located in exon 2 (coding exon 2) of the ZNF559 gene. This alteration results from a C to T substitution at nucleotide position 97, causing the proline (P) at amino acid position 33 to be replaced by a serine (S). 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

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.8

DANN

Benign

0.82

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.0051

T;T

PrimateAI

Benign

0.34

Sift4G

Benign

0.099

T;T

Vest4

0.18

MVP

0.18

GERP RS

-0.015

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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