14-21091887-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016423.3(ZNF219):​c.1410G>T​(p.Gln470His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF219
NM_016423.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.937
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1794872).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF219NM_016423.3 linkuse as main transcriptc.1410G>T p.Gln470His missense_variant 3/5 ENST00000360947.8 NP_057507.2 Q9P2Y4
ZNF219NM_001101672.2 linkuse as main transcriptc.1410G>T p.Gln470His missense_variant 3/5 NP_001095142.1 Q9P2Y4
ZNF219NM_001102454.2 linkuse as main transcriptc.1410G>T p.Gln470His missense_variant 3/5 NP_001095924.1 Q9P2Y4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF219ENST00000360947.8 linkuse as main transcriptc.1410G>T p.Gln470His missense_variant 3/51 NM_016423.3 ENSP00000354206.3 Q9P2Y4
ZNF219ENST00000421093.6 linkuse as main transcriptc.1410G>T p.Gln470His missense_variant 3/51 ENSP00000392401.2 Q9P2Y4
ZNF219ENST00000451119.6 linkuse as main transcriptc.1410G>T p.Gln470His missense_variant 3/55 ENSP00000388558.2 Q9P2Y4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsJul 12, 2023The c.1410G>T (p.Q470H) alteration is located in exon 3 (coding exon 2) of the ZNF219 gene. This alteration results from a G to T substitution at nucleotide position 1410, causing the glutamine (Q) at amino acid position 470 to be replaced by a histidine (H). 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
0.19
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0032
T;T;T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.70
.;.;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.81
L;L;L
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.74
N;N;N
REVEL
Benign
0.051
Sift
Benign
0.060
T;T;T
Sift4G
Benign
0.096
T;T;T
Polyphen
0.98
D;D;D
Vest4
0.21
MutPred
0.26
Gain of solvent accessibility (P = 0.0012);Gain of solvent accessibility (P = 0.0012);Gain of solvent accessibility (P = 0.0012);
MVP
0.068
MPC
1.4
ClinPred
0.38
T
GERP RS
1.4
Varity_R
0.091
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1256490530; hg19: chr14-21560046; API