Variant 14-21090987-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016423.3(ZNF219):c.1718C>T(p.Ala573Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,549,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

ZNF219
NM_016423.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.115

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04993829).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF219	NM_016423.3 linkuse as main transcript	c.1718C>T	p.Ala573Val	missense_variant	5/5	ENST00000360947.8	NP_057507.2	Q9P2Y4
ZNF219	NM_001101672.2 linkuse as main transcript	c.1718C>T	p.Ala573Val	missense_variant	5/5		NP_001095142.1	Q9P2Y4
ZNF219	NM_001102454.2 linkuse as main transcript	c.1718C>T	p.Ala573Val	missense_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.1718C>T	p.Ala573Val	missense_variant	5/5	1	NM_016423.3	ENSP00000354206.3	Q9P2Y4
ZNF219	ENST00000421093.6 linkuse as main transcript	c.1718C>T	p.Ala573Val	missense_variant	5/5	1		ENSP00000392401.2	Q9P2Y4
ZNF219	ENST00000451119.6 linkuse as main transcript	c.1718C>T	p.Ala573Val	missense_variant	5/5	5		ENSP00000388558.2	Q9P2Y4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

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

GnomAD4 exome

AF:

0.00000644

AC:

AN:

1397116

Hom.:

Cov.:

AF XY:

0.00000868

AC XY:

AN XY:

691102

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000829

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.1718C>T (p.A573V) alteration is located in exon 5 (coding exon 4) of the ZNF219 gene. This alteration results from a C to T substitution at nucleotide position 1718, causing the alanine (A) at amino acid position 573 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.1

DANN

Benign

0.94

DEOGEN2

Benign

0.016

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.64

.;.;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.010

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.026

MutPred

0.25

Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);

MVP

0.043

MPC

0.77

ClinPred

0.055

GERP RS

0.87

Varity_R

0.028

gMVP

0.38

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