19-42224484-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_133444.3(ZNF526):c.81G>A(p.Ser27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,614,060 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: ZNF526 NM_133444.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.50

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF526	NM_133444.3	c.81G>A	p.Ser27=	synonymous_variant	3/3	ENST00000301215.8
ZNF526	NM_001314033.3	c.81G>A	p.Ser27=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF526	ENST00000301215.8	c.81G>A	p.Ser27=	synonymous_variant	3/3	1	NM_133444.3	P1
ZNF526	ENST00000710326.1	c.81G>A	p.Ser27=	synonymous_variant	3/3			P1
ZNF526	ENST00000597945.1	c.81G>A	p.Ser27=	synonymous_variant	3/3	4

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152172 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000620 AC: 156 AN: 251488 Hom.: 0 AF XY: 0.000603 AC XY: 82 AN XY: 135918

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00118

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00132 AC: 1926 AN: 1461888 Hom.: 2 Cov.: 30 AF XY: 0.00128 AC XY: 928 AN XY: 727246

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00167

Gnomad4 OTH exome AF: 0.000546

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152172 Hom.: 0 Cov.: 31 AF XY: 0.000592 AC XY: 44 AN XY: 74328

Gnomad4 AFR AF: 0.000410

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.000676

EpiCase AF: 0.00115

EpiControl AF: 0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 01, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.37

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: rs149913848; hg19: chr19-42728636; COSMIC: COSV56629117; COSMIC: COSV56629117;