rs367731450

Variant names:

• chr19-42225153-TGAG-T
• rs367731450
• NM_133444.3:c.755_757delAGG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_133444.3(ZNF526):​c.755_757delAGG​(p.Glu252del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00483 in 1,614,042 control chromosomes in the GnomAD database, including 292 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E252E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.026 (172 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (120 hom.)
• Consequence: ZNF526 NM_133444.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.46
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ENSG00000288671 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 19-42225153-TGAG-T is Benign according to our data. Variant chr19-42225153-TGAG-T is described in ClinVar as Benign. ClinVar VariationId is 212686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

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.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3	NP_597701.1	H9ZYJ3
	ZNF526	NM_001314033.3		c.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3	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.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3	ENSP00000301215.2	Q8TF50
	ENSG00000288671	ENST00000678490.1		c.91+6901_91+6903delCTC		intron	N/A	ENSP00000502878.1	A0A7I2V2F5
	ZNF526	ENST00000710326.1		c.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3	ENSP00000518206.1	Q8TF50

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3925 AN: 152062 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00664 AC: 1668 AN: 251200 AF XY: 0.00497

Gnomad AFR exome AF: 0.0892

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00264 AC: 3864 AN: 1461862 Hom.: 120 AF XY: 0.00235 AC XY: 1711 AN XY: 727222

African (AFR) AF: 0.0882 AC: 2952 AN: 33478

American (AMR) AF: 0.00510 AC: 228 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.000219 AC: 243 AN: 1111992

Other (OTH) AF: 0.00664 AC: 401 AN: 60390

GnomAD4 genome AF: 0.0259 AC: 3934 AN: 152180 Hom.: 172 Cov.: 32 AF XY: 0.0246 AC XY: 1833 AN XY: 74392

African (AFR) AF: 0.0891 AC: 3700 AN: 41530

American (AMR) AF: 0.0105 AC: 160 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 67980

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0148 Hom.: 13

Bravo AF: 0.0297

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	ZNF526-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=88/12	polymorphism (auto)

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: rs367731450; hg19: chr19-42729305; COSMIC: COSV106435800; COSMIC: COSV106435800;