19-44234896-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000313040.12(ZNF227):​c.466C>G​(p.Pro156Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF227
ENST00000313040.12 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.542
Variant links:
Genes affected
ZNF227 (HGNC:13020): (zinc finger protein 227) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
ZNF235 (HGNC:12866): (zinc finger protein 235) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein is a member of the Kruppel family of zinc finger proteins, and contains Kruppel-associated box (KRAB) A and B domains and 15 tandemly arrayed C2H2-type zinc fingers. It is an ortholog of the mouse Zfp93 protein. This gene is located in a cluster of zinc finger genes on 19q13.2. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.045163274).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF227NM_182490.3 linkuse as main transcriptc.466C>G p.Pro156Ala missense_variant 6/6 ENST00000313040.12 NP_872296.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF227ENST00000313040.12 linkuse as main transcriptc.466C>G p.Pro156Ala missense_variant 6/61 NM_182490.3 ENSP00000321049 P1Q86WZ6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 GeneticsApr 03, 2023The c.466C>G (p.P156A) alteration is located in exon 6 (coding exon 4) of the ZNF227 gene. This alteration results from a C to G substitution at nucleotide position 466, causing the proline (P) at amino acid position 156 to be replaced by an alanine (A). 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
0.074
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.064
DANN
Benign
0.47
DEOGEN2
Benign
0.015
.;T;.;T;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.19
T;T;T;.;T;.
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.045
T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.26
.;N;.;N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
0.23
N;.;.;N;.;.
REVEL
Benign
0.024
Sift
Benign
0.53
T;.;.;T;.;.
Sift4G
Benign
0.97
T;T;T;T;T;T
Polyphen
0.0020
.;B;.;B;.;.
Vest4
0.060
MutPred
0.23
.;Loss of stability (P = 0.0499);.;Loss of stability (P = 0.0499);.;.;
MVP
0.095
MPC
0.095
ClinPred
0.017
T
GERP RS
0.91
Varity_R
0.026
gMVP
0.035

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-44739049; API