chr14-21092593-G-GGAGGCT

Position:

• chr14-21092593-G-GGAGGCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016423.3(ZNF219):​c.698_703dupAGCCTC​(p.Gln233_Pro234dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,547,654 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: ZNF219 NM_016423.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF219	NM_016423.3	c.698_703dupAGCCTC	p.Gln233_Pro234dup	conservative_inframe_insertion	3/5	ENST00000360947.8	NP_057507.2
ZNF219	NM_001101672.2	c.698_703dupAGCCTC	p.Gln233_Pro234dup	conservative_inframe_insertion	3/5		NP_001095142.1
ZNF219	NM_001102454.2	c.698_703dupAGCCTC	p.Gln233_Pro234dup	conservative_inframe_insertion	3/5		NP_001095924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF219	ENST00000360947.8	c.698_703dupAGCCTC	p.Gln233_Pro234dup	conservative_inframe_insertion	3/5	1	NM_016423.3	ENSP00000354206.3
ZNF219	ENST00000421093.6	c.698_703dupAGCCTC	p.Gln233_Pro234dup	conservative_inframe_insertion	3/5	1		ENSP00000392401.2
ZNF219	ENST00000451119.6	c.698_703dupAGCCTC	p.Gln233_Pro234dup	conservative_inframe_insertion	3/5	5		ENSP00000388558.2

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 151776 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000969

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.000240 AC: 35 AN: 145600 Hom.: 0 AF XY: 0.000255 AC XY: 20 AN XY: 78458

Gnomad AFR exome AF: 0.000136

Gnomad AMR exome AF: 0.000163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000882

Gnomad SAS exome AF: 0.0000438

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000307

Gnomad OTH exome AF: 0.000477

GnomAD4 exome AF: 0.000278 AC: 388 AN: 1395758 Hom.: 0 Cov.: 29 AF XY: 0.000269 AC XY: 185 AN XY: 688732

Gnomad4 AFR exome AF: 0.000156

Gnomad4 AMR exome AF: 0.000140

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000496

Gnomad4 SAS exome AF: 0.0000756

Gnomad4 FIN exome AF: 0.0000458

Gnomad4 NFE exome AF: 0.000305

Gnomad4 OTH exome AF: 0.000396

GnomAD4 genome AF: 0.000171 AC: 26 AN: 151896 Hom.: 0 Cov.: 29 AF XY: 0.000215 AC XY: 16 AN XY: 74252

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000972

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.000476

Bravo AF: 0.000170

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;