ENST00000597078.5:c.349+1437G>A

Variant names:

• chr19-21543323-G-A
• rs2681384
• ENST00000597078.5:c.349+1437G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000597078.5(ZNF429):​c.349+1437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,964 control chromosomes in the GnomAD database, including 2,646 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 0.18 (2646 hom., cov: 32)
• Consequence: ZNF429 ENST00000597078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 15 publications found

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]

ENSG00000268081 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF429	ENST00000597078.5	c.349+1437G>A		intron_variant	Intron 4 of 5	1		ENSP00000470300.1
ZNF429	ENST00000594385.1	c.121+1437G>A		intron_variant	Intron 1 of 1	1		ENSP00000469739.1
ENSG00000268081	ENST00000804915.1	n.171C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28094 AN: 151846 Hom.: 2645 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.185 AC: 28099 AN: 151964 Hom.: 2646 Cov.: 32 AF XY: 0.185 AC XY: 13743 AN XY: 74248

African (AFR) AF: 0.182 AC: 7554 AN: 41442

American (AMR) AF: 0.175 AC: 2664 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3472

East Asian (EAS) AF: 0.0769 AC: 397 AN: 5162

South Asian (SAS) AF: 0.181 AC: 871 AN: 4810

European-Finnish (FIN) AF: 0.192 AC: 2020 AN: 10540

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13139 AN: 67986

Other (OTH) AF: 0.185 AC: 391 AN: 2110

Alfa AF: 0.193 Hom.: 1534

Bravo AF: 0.185

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.48
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2681384; hg19: chr19-21726125;