Genetic Variant ZNF219:p.Gln231_Pro234dup (chr14-21092593-G-GGAGGCTGAGGCT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_016423.3(ZNF219):c.692_703dupAGCCTCAGCCTC(p.Gln231_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 0.00000323 in 1,547,534 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 INS_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: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ZNF219
NM_016423.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.447

Publications

9 publications found

Variant links:

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

ZNF219 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ZNF219	NM_016423.3 link	c.692_703dupAGCCTCAGCCTC	p.Gln231_Pro234dup	conservative_inframe_insertion	Exon 3 of 5	ENST00000360947.8	NP_057507.2
ZNF219	NM_001101672.2 link	c.692_703dupAGCCTCAGCCTC	p.Gln231_Pro234dup	conservative_inframe_insertion	Exon 3 of 5		NP_001095142.1
ZNF219	NM_001102454.2 link	c.692_703dupAGCCTCAGCCTC	p.Gln231_Pro234dup	conservative_inframe_insertion	Exon 3 of 5		NP_001095924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ZNF219	ENST00000360947.8 link	c.692_703dupAGCCTCAGCCTC	p.Gln231_Pro234dup	conservative_inframe_insertion	Exon 3 of 5	1	NM_016423.3	ENSP00000354206.3
ZNF219	ENST00000421093.6 link	c.692_703dupAGCCTCAGCCTC	p.Gln231_Pro234dup	conservative_inframe_insertion	Exon 3 of 5	1		ENSP00000392401.2
ZNF219	ENST00000451119.6 link	c.692_703dupAGCCTCAGCCTC	p.Gln231_Pro234dup	conservative_inframe_insertion	Exon 3 of 5	5		ENSP00000388558.2
ZNF219	ENST00000555270.5 link	c.58_69dupAGCCTCAGCCTC		downstream_gene_variant		4		ENSP00000450803.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000687

AC:

AN:

145600

AF XY:

0.0000127

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1395758

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

688732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31956

American (AMR)

AF:

0.00

AC:

AN:

35760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

36320

South Asian (SAS)

AF:

0.00

AC:

AN:

79398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1080032

Other (OTH)

AF:

0.0000345

AC:

AN:

58020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41278

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67906

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000451

Hom.:

247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.45

Mutation Taster

=77/23

polymorphism

(source)

Splicing

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

Publications

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14-21092593-GGAGGCTGAGGCT-GGAGGCTGAGGCTGAGGCTGAGGCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over