Variant 14-21090934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016423.3(ZNF219):c.1771G>A(p.Ala591Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000861 in 1,393,970 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

ZNF219
NM_016423.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.310

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024128437).

BP6

Variant 14-21090934-C-T is Benign according to our data. Variant chr14-21090934-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3335152.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF219	NM_016423.3 linkuse as main transcript	c.1771G>A	p.Ala591Thr	missense_variant	5/5	ENST00000360947.8	NP_057507.2	Q9P2Y4
ZNF219	NM_001101672.2 linkuse as main transcript	c.1771G>A	p.Ala591Thr	missense_variant	5/5		NP_001095142.1	Q9P2Y4
ZNF219	NM_001102454.2 linkuse as main transcript	c.1771G>A	p.Ala591Thr	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.1771G>A	p.Ala591Thr	missense_variant	5/5	1	NM_016423.3	ENSP00000354206.3	Q9P2Y4
ZNF219	ENST00000421093.6 linkuse as main transcript	c.1771G>A	p.Ala591Thr	missense_variant	5/5	1		ENSP00000392401.2	Q9P2Y4
ZNF219	ENST00000451119.6 linkuse as main transcript	c.1771G>A	p.Ala591Thr	missense_variant	5/5	5		ENSP00000388558.2	Q9P2Y4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000209

AC:

AN:

143218

Hom.:

AF XY:

0.0000383

AC XY:

AN XY:

78312

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000861

AC:

AN:

1393970

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

688716

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:

0.0000102

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.39

DANN

Benign

0.85

DEOGEN2

Benign

0.0042

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.63

.;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.20

N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.20

N;N;N

REVEL

Benign

0.010

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.69

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.040

MutPred

0.29

Gain of phosphorylation at A591 (P = 0.0123);Gain of phosphorylation at A591 (P = 0.0123);Gain of phosphorylation at A591 (P = 0.0123);

MVP

0.043

MPC

0.75

ClinPred

0.037

GERP RS

-0.38

Varity_R

0.033

gMVP

0.25

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