19-52415231-AG-A

Position:

• chr19-52415231-AG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_032423.3(ZNF528):​c.381del​(p.Ile129PhefsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,614,134 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (5 hom.)
• Consequence: ZNF528 NM_032423.3 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226

Genes affected

ZNF528 (HGNC:29384): (zinc finger protein 528) 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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-52415231-AG-A is Benign according to our data. Variant chr19-52415231-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 771528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF528	NM_032423.3	c.381del	p.Ile129PhefsTer32	frameshift_variant	7/7	ENST00000360465.8	NP_115799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF528	ENST00000360465.8	c.381del	p.Ile129PhefsTer32	frameshift_variant	7/7	1	NM_032423.3	ENSP00000353652	P1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 249 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00200 AC: 501 AN: 251012 Hom.: 1 AF XY: 0.00197 AC XY: 267 AN XY: 135786

Gnomad AFR exome AF: 0.000497

Gnomad AMR exome AF: 0.00336

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000832

Gnomad NFE exome AF: 0.00271

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00208 AC: 3038 AN: 1461774 Hom.: 5 Cov.: 32 AF XY: 0.00204 AC XY: 1487 AN XY: 727170

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00342

Gnomad4 ASJ exome AF: 0.00279

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00118

Gnomad4 NFE exome AF: 0.00232

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.00163 AC: 249 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.00150 AC XY: 112 AN XY: 74520

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000470

Gnomad4 NFE AF: 0.00245

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000839 Hom.: 0

Bravo AF: 0.00190

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00289

EpiControl AF: 0.00290

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

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: rs562901913; hg19: chr19-52918484;