Genetic Variant ZNF527:p.Pro301LeufsTer7 (chr19-37388950-C-CTGTG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_032453.2(ZNF527):c.901_902insTGTG(p.Pro301LeufsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,964 control chromosomes in the GnomAD database, including 16,493 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1181 hom., cov: 31)

Exomes 𝑓: 0.14 ( 15312 hom. )

Consequence

ZNF527
NM_032453.2 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

ZNF527 (HGNC:29385): (zinc finger protein 527) 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]

ZNF527 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 19-37388950-C-CTGTG is Benign according to our data. Variant chr19-37388950-C-CTGTG is described in ClinVar as [Benign]. Clinvar id is 773354.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF527	NM_032453.2 link	c.901_902insTGTG	p.Pro301LeufsTer7	frameshift_variant	Exon 5 of 5	ENST00000436120.7	NP_115829.1	Q8NB42-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF527	ENST00000436120.7 link	c.901_902insTGTG	p.Pro301LeufsTer7	frameshift_variant	Exon 5 of 5	4	NM_032453.2	ENSP00000390179.2		Q8NB42-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16927

AN:

152016

Hom.:

1182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.0800

Gnomad SAS

AF:

0.0785

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.0338

AC:

7504

AN:

222140

Hom.:

852

AF XY:

0.0373

AC XY:

4488

AN XY:

120234

show subpopulations

Gnomad AFR exome

AF:

0.00530

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0516

Gnomad EAS exome

AF:

0.0132

Gnomad SAS exome

AF:

0.0245

Gnomad FIN exome

AF:

0.0320

Gnomad NFE exome

AF:

0.0509

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.140

AC:

204755

AN:

1461830

Hom.:

15312

Cov.:

AF XY:

0.139

AC XY:

101279

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0258

Gnomad4 AMR exome

AF:

0.0738

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.0777

Gnomad4 SAS exome

AF:

0.0851

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.111

AC:

16918

AN:

152134

Hom.:

1181

Cov.:

AF XY:

0.109

AC XY:

8125

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.0801

Gnomad4 SAS

AF:

0.0784

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.106

Hom.:

212

Bravo

AF:

0.104

Asia WGS

AF:

0.101

AC:

351

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over