chr19-9324741-C-T

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

10

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-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]

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
ZNF559NM_032497.3 linkc.-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
ZNF559ENST00000603380 linkc.-159C>T 5_prime_UTR_variant 2/72 NM_032497.3 ENSP00000474760.1 Q9BR84-1
ZNF559-ZNF177ENST00000541595 linkc.-519C>T 5_prime_UTR_variant 2/122 ENSP00000445323.1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
151932
Hom.:
0
Cov.:
31
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:
36
AN:
134662
Hom.:
0
AF XY:
0.000245
AC XY:
18
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.:
1
Cov.:
33
AF XY:
0.0000747
AC XY:
51
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:
9
AN:
151932
Hom.:
0
Cov.:
31
AF XY:
0.0000809
AC XY:
6
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.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.000107
AC:
2

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 submitterclinical testingAmbry GeneticsDec 28, 2023The 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
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
7.8
DANN
Benign
0.82
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.0051
T;T
PrimateAI
Benign
0.34
T
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.

Other links and lift over

dbSNP: rs759368485; hg19: chr19-9435417; API