Variant 14-21091082-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016423.3(ZNF219):c.1623C>G(p.Leu541Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00765 in 1,571,172 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 50 hom. )

Consequence

ZNF219
NM_016423.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0840

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 14-21091082-G-C is Benign according to our data. Variant chr14-21091082-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644056.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.084 with no splicing effect.

BS2

High AC in GnomAd4 at 842 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF219	NM_016423.3 linkuse as main transcript	c.1623C>G	p.Leu541Leu	synonymous_variant	5/5	ENST00000360947.8	NP_057507.2	Q9P2Y4
ZNF219	NM_001101672.2 linkuse as main transcript	c.1623C>G	p.Leu541Leu	synonymous_variant	5/5		NP_001095142.1	Q9P2Y4
ZNF219	NM_001102454.2 linkuse as main transcript	c.1623C>G	p.Leu541Leu	synonymous_variant	5/5		NP_001095924.1	Q9P2Y4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF219	ENST00000360947.8 linkuse as main transcript	c.1623C>G	p.Leu541Leu	synonymous_variant	5/5	1	NM_016423.3	ENSP00000354206.3	Q9P2Y4
ZNF219	ENST00000421093.6 linkuse as main transcript	c.1623C>G	p.Leu541Leu	synonymous_variant	5/5	1		ENSP00000392401.2	Q9P2Y4
ZNF219	ENST00000451119.6 linkuse as main transcript	c.1623C>G	p.Leu541Leu	synonymous_variant	5/5	5		ENSP00000388558.2	Q9P2Y4

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

842

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00893

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00484

AC:

842

AN:

173828

Hom.:

AF XY:

0.00489

AC XY:

469

AN XY:

95858

show subpopulations

Gnomad AFR exome

AF:

0.000977

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000465

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00151

Gnomad FIN exome

AF:

0.00955

Gnomad NFE exome

AF:

0.00856

Gnomad OTH exome

AF:

0.00401

GnomAD4 exome

AF:

0.00788

AC:

11185

AN:

1418884

Hom.:

Cov.:

AF XY:

0.00767

AC XY:

5393

AN XY:

703092

show subpopulations

Gnomad4 AFR exome

AF:

0.000976

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.000276

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.00925

Gnomad4 OTH exome

AF:

0.00586

GnomAD4 genome

AF:

0.00553

AC:

842

AN:

152288

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00202

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0129

Gnomad4 NFE

AF:

0.00893

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00610

Hom.:

Bravo

AF:

0.00447

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ZNF219: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.0

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over