Genetic Variant ZNF559:c.-194C>G (chr19-9324706-C-G) – 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_032497.3(ZNF559):c.-194C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000507 in 1,381,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

ZNF559
NM_032497.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.943

Publications

0 publications found

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:

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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=0.078368396).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032497.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF559	NM_032497.3	MANE Select	c.-194C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_115886.1	Q9BR84-1
ZNF559	NM_032497.3	MANE Select	c.-194C>G	5_prime_UTR	Exon 2 of 7	NP_115886.1	Q9BR84-1
ZNF559	NM_001202407.3		c.-267C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001189336.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF559	ENST00000603380.6	TSL:2 MANE Select	c.-194C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000474760.1	Q9BR84-1
ZNF559-ZNF177	ENST00000541595.6	TSL:2	c.-554C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000445323.1
ZNF559	ENST00000586255.5	TSL:1	c.-269C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000465787.2	K7EKU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000507

AC:

AN:

1381642

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

681804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31334

American (AMR)

AF:

0.00

AC:

AN:

35598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25076

East Asian (EAS)

AF:

0.00

AC:

AN:

35620

South Asian (SAS)

AF:

0.00

AC:

AN:

79196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00000650

AC:

AN:

1077702

Other (OTH)

AF:

0.00

AC:

AN:

57708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.7

(source)

DANN

Benign

0.24

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.32

M_CAP

Benign

0.00082

MetaRNN

Benign

0.078

PhyloP100

-0.94

PrimateAI

Benign

0.42

Sift4G

Uncertain

0.027

Vest4

0.20

MVP

0.16

GERP RS

-0.20

PromoterAI

0.028

Neutral

(source)

gMVP

0.37

Mutation Taster

=299/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over