rs367731450

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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 (★★).

• 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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF526	NM_133444.3	c.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3	ENST00000301215.8	NP_597701.1
ZNF526	NM_001314033.3	c.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3		NP_001300962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF526	ENST00000301215.8	c.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3	1	NM_133444.3	ENSP00000301215.2
ENSG00000288671	ENST00000678490.1	c.91+6901_91+6903delCTC		intron_variant	Intron 1 of 1			ENSP00000502878.1
ZNF526	ENST00000710326.1	c.755_757delAGG	p.Glu252del	disruptive_inframe_deletion	Exon 3 of 3			ENSP00000518206.1

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

GnomAD3 exomes AF: 0.00664 AC: 1668 AN: 251200 Hom.: 55 AF XY: 0.00497 AC XY: 675 AN XY: 135788

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 SAS exome AF: 0.000261

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

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.00510

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00664

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

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0170

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Aug 16, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ZNF526-related disorder Benign:1

Feb 07, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs367731450; hg19: chr19-42729305;