19-42226075-CGC-TGT

Variant names:

• chr19-42226075-CGC-TGT
• NM_133444.3:c.1672_1674delCGCinsTGT
• ZNF526 p.Arg558Cys

Variant summary

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

The NM_133444.3(ZNF526):​c.1672_1674delCGCinsTGT​(p.Arg558Cys) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF526 NM_133444.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• Publications: 0 publications found

Genes affected

ZNF526 (HGNC:29415): (zinc finger protein 526) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288671 (HGNC:):

GSK3A (HGNC:4616): (glycogen synthase kinase 3 alpha) This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133444.3. 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
	ZNF526	NM_133444.3	MANE Select	c.1672_1674delCGCinsTGT	p.Arg558Cys	missense	N/A	NP_597701.1	H9ZYJ3
	ZNF526	NM_001314033.3		c.1672_1674delCGCinsTGT	p.Arg558Cys	missense	N/A	NP_001300962.1	H9ZYJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF526	ENST00000301215.8	TSL:1 MANE Select	c.1672_1674delCGCinsTGT	p.Arg558Cys	missense	N/A	ENSP00000301215.2	Q8TF50
	ENSG00000288671	ENST00000678490.1		c.91+5980_91+5982delGCGinsACA		intron	N/A	ENSP00000502878.1	A0A7I2V2F5
	ZNF526	ENST00000710326.1		c.1672_1674delCGCinsTGT	p.Arg558Cys	missense	N/A	ENSP00000518206.1	Q8TF50

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59

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: chr19-42730227;