NM_133444.3:c.750_752delTGA

Variant names:

• chr19-42225150-GGAT-G
• rs587780524
• NM_133444.3:c.750_752delTGA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_133444.3(ZNF526):​c.750_752delTGA​(p.Asp250del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF526 NM_133444.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51
• 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]

ZNF526 Gene-Disease associations (from GenCC):

• Dentici-Novelli neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000288671 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF526	NM_133444.3	MANE Select	c.750_752delTGA	p.Asp250del	disruptive_inframe_deletion	Exon 3 of 3	NP_597701.1
	ZNF526	NM_001314033.3		c.750_752delTGA	p.Asp250del	disruptive_inframe_deletion	Exon 3 of 3	NP_001300962.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF526	ENST00000301215.8	TSL:1 MANE Select	c.750_752delTGA	p.Asp250del	disruptive_inframe_deletion	Exon 3 of 3	ENSP00000301215.2
	ENSG00000288671	ENST00000678490.1		c.91+6904_91+6906delATC		intron	N/A	ENSP00000502878.1
	ZNF526	ENST00000710326.1		c.750_752delTGA	p.Asp250del	disruptive_inframe_deletion	Exon 3 of 3	ENSP00000518206.1

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

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

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

Other links and lift over

dbSNP: rs587780524; hg19: chr19-42729302;