14-21092593-GGAGGCTGAGGCT-GGAGGCT

Variant names:

• chr14-21092593-GGAGGCT-G
• rs3841049
• NM_016423.3:c.698_703delAGCCTC

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ZNF219 Gene-Disease associations (from GenCC):

• microphthalmia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016423.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF219	NM_016423.3	MANE Select	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	NP_057507.2
	ZNF219	NM_001101672.2		c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	NP_001095142.1
	ZNF219	NM_001102454.2		c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	NP_001095924.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF219	ENST00000360947.8	TSL:1 MANE Select	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	ENSP00000354206.3
	ZNF219	ENST00000421093.6	TSL:1	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	ENSP00000392401.2
	ZNF219	ENST00000451119.6	TSL:5	c.698_703delAGCCTC	p.Gln233_Pro234del	disruptive_inframe_deletion	Exon 3 of 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

GnomAD2 exomes AF: 0.226 AC: 32850 AN: 145600 AF XY: 0.222

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 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

African (AFR) AF: 0.267 AC: 8534 AN: 31948

American (AMR) AF: 0.390 AC: 13957 AN: 35754

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4344 AN: 25166

East Asian (EAS) AF: 0.128 AC: 4633 AN: 36320

South Asian (SAS) AF: 0.270 AC: 21405 AN: 79390

European-Finnish (FIN) AF: 0.0994 AC: 4342 AN: 43696

Middle Eastern (MID) AF: 0.189 AC: 1017 AN: 5388

European-Non Finnish (NFE) AF: 0.193 AC: 208863 AN: 1079980

Other (OTH) AF: 0.199 AC: 11560 AN: 58016

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

African (AFR) AF: 0.258 AC: 10662 AN: 41360

American (AMR) AF: 0.333 AC: 5083 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3472

East Asian (EAS) AF: 0.129 AC: 666 AN: 5144

South Asian (SAS) AF: 0.287 AC: 1380 AN: 4808

European-Finnish (FIN) AF: 0.0937 AC: 994 AN: 10604

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

European-Non Finnish (NFE) AF: 0.193 AC: 13070 AN: 67880

Other (OTH) AF: 0.203 AC: 427 AN: 2102

Alfa AF: 0.113 Hom.: 247

Bravo AF: 0.234

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70
Mutation Taster		=199/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3841049; hg19: chr14-21560752; COSMIC: COSV53877928; COSMIC: COSV53877928;