14-21092593-GGAGGCTGAGGCT-GGAGGCT

Position:

• chr14-21092593-GGAGGCTGAGGCT-GGAGGCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016423.3(ZNF219):​c.698_703delAGCCTC​(p.Gln233_Pro234del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,547,478 control chromosomes in the GnomAD database, including 33,501 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (3930 hom., cov: 28)
  • Exomes 𝑓: 0.20 (29571 hom.)
• Consequence: ZNF219 NM_016423.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.699

Genes affected

ZNF219 (HGNC:13011): (zinc finger protein 219) This gene is a member of the Kruppel-like zinc finger gene family. The encoded protein functions as a transcriptional repressor of the high mobility group nucleosome binding domain 1 protein, which is associated with transcriptionally active chromatin. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF219	NM_016423.3	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	3/5	ENST00000360947.8	NP_057507.2
ZNF219	NM_001101672.2	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	3/5		NP_001095142.1
ZNF219	NM_001102454.2	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	3/5		NP_001095924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF219	ENST00000360947.8	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	3/5	1	NM_016423.3	ENSP00000354206.3
ZNF219	ENST00000421093.6	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	3/5	1		ENSP00000392401.2
ZNF219	ENST00000451119.6	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	3/5	5		ENSP00000388558.2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32979 AN: 151700 Hom.: 3928 Cov.: 28

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.226 AC: 32850 AN: 145600 Hom.: 4511 AF XY: 0.222 AC XY: 17421 AN XY: 78458

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.266

Gnomad FIN exome AF: 0.0887

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.200 AC: 278655 AN: 1395658 Hom.: 29571 AF XY: 0.201 AC XY: 138743 AN XY: 688680

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.0994

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.218 AC: 33023 AN: 151820 Hom.: 3930 Cov.: 28 AF XY: 0.216 AC XY: 16006 AN XY: 74212

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.203

Bravo AF: 0.234

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3841049; hg19: chr14-21560752;