chr14-21092593-GGAGGCTGAGGCT-G

Variant names:

• chr14-21092593-GGAGGCTGAGGCT-G
• rs3841049
• NM_016423.3:c.692_703delAGCCTCAGCCTC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016423.3(ZNF219):​c.692_703delAGCCTCAGCCTC​(p.Gln231_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 0.00000788 in 1,395,756 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: ZNF219 NM_016423.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF219	NM_016423.3	c.692_703delAGCCTCAGCCTC	p.Gln231_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	ENST00000360947.8	NP_057507.2
ZNF219	NM_001101672.2	c.692_703delAGCCTCAGCCTC	p.Gln231_Pro234del	disruptive_inframe_deletion	Exon 3 of 5		NP_001095142.1
ZNF219	NM_001102454.2	c.692_703delAGCCTCAGCCTC	p.Gln231_Pro234del	disruptive_inframe_deletion	Exon 3 of 5		NP_001095924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF219	ENST00000360947.8	c.692_703delAGCCTCAGCCTC	p.Gln231_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	1	NM_016423.3	ENSP00000354206.3
ZNF219	ENST00000421093.6	c.692_703delAGCCTCAGCCTC	p.Gln231_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	1		ENSP00000392401.2
ZNF219	ENST00000451119.6	c.692_703delAGCCTCAGCCTC	p.Gln231_Pro234del	disruptive_inframe_deletion	Exon 3 of 5	5		ENSP00000388558.2
ZNF219	ENST00000555270.5	c.*58_*69delAGCCTCAGCCTC		downstream_gene_variant		4		ENSP00000450803.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000788 AC: 11 AN: 1395756 Hom.: 0 AF XY: 0.00000871 AC XY: 6 AN XY: 688730

African (AFR) AF: 0.00 AC: 0 AN: 31956

American (AMR) AF: 0.0000280 AC: 1 AN: 35760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 36320

South Asian (SAS) AF: 0.00 AC: 0 AN: 79398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5392

European-Non Finnish (NFE) AF: 0.00000926 AC: 10 AN: 1080032

Other (OTH) AF: 0.00 AC: 0 AN: 58020

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 247

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

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;