19-21522243-C-T

Position:

• chr19-21522243-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001415.4(ZNF429):​c.4-7415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,192 control chromosomes in the GnomAD database, including 2,100 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2100 hom., cov: 32)
• Consequence: ZNF429 NM_001001415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

Genes affected

ZNF429 (HGNC:20817): (zinc finger protein 429) 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]

ZNF429 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF429	NM_001001415.4	c.4-7415C>T		intron_variant		ENST00000358491.9	NP_001001415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF429	ENST00000358491.9	c.4-7415C>T		intron_variant		3	NM_001001415.4	ENSP00000351280.3
ZNF429	ENST00000597078.5	c.4-7415C>T		intron_variant		1		ENSP00000470300.1
ZNF429	ENST00000594022.1	n.193-6841C>T		intron_variant		3
ZNF429	ENST00000596126.1	n.469-6841C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24758 AN: 152074 Hom.: 2103 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.170

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.163 AC: 24754 AN: 152192 Hom.: 2100 Cov.: 32 AF XY: 0.163 AC XY: 12164 AN XY: 74398

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0766

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.167

Alfa AF: 0.177 Hom.: 2485

Bravo AF: 0.161

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.91

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: rs11085455; hg19: chr19-21705045;