19-9341804-CC-AT

Variant names:

• chr19-9341804-CC-AT
• NM_032497.3:c.353_354delCCinsAT
• ZNF559 p.Thr118Asn

Variant summary

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

The NM_032497.3(ZNF559):​c.353_354delCCinsAT​(p.Thr118Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T118I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF559 NM_032497.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 0 publications found

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]

ENSG00000283108 (HGNC:):

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF559	NM_032497.3	MANE Select	c.353_354delCCinsAT	p.Thr118Asn	missense	N/A	NP_115886.1	Q9BR84-1
	ZNF559	NM_001202406.1		c.545_546delCCinsAT	p.Thr182Asn	missense	N/A	NP_001189335.1	A0A0A0MTT2
	ZNF559	NM_001202407.3		c.227_228delCCinsAT	p.Thr76Asn	missense	N/A	NP_001189336.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF559	ENST00000603380.6	TSL:2 MANE Select	c.353_354delCCinsAT	p.Thr118Asn	missense	N/A	ENSP00000474760.1	Q9BR84-1
	ZNF559	ENST00000592896.5	TSL:1	c.*176_*177delCCinsAT		3_prime_UTR	Exon 7 of 7	ENSP00000466496.2	A0A0A0MTS4
	ZNF559	ENST00000585352.5	TSL:1	c.*176_*177delCCinsAT		3_prime_UTR	Exon 6 of 6	ENSP00000467048.1	Q9BR84-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-9452480;