19-44235301-C-T

Variant summary

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

The NM_182490.3(ZNF227):​c.871C>T​(p.His291Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF227
NM_182490.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98
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]

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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=0.19308075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF227NM_182490.3 linkc.871C>T p.His291Tyr missense_variant Exon 6 of 6 ENST00000313040.12 NP_872296.1 Q86WZ6-1Q658S5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF227ENST00000313040.12 linkc.871C>T p.His291Tyr missense_variant Exon 6 of 6 1 NM_182490.3 ENSP00000321049.6 Q86WZ6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
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
Apr 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.871C>T (p.H291Y) alteration is located in exon 6 (coding exon 4) of the ZNF227 gene. This alteration results from a C to T substitution at nucleotide position 871, causing the histidine (H) at amino acid position 291 to be replaced by a tyrosine (Y). 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
0.069
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
.;T;T;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.33
T;T;.;.
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.19
T;T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Pathogenic
3.2
.;M;M;.
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.3
D;.;D;.
REVEL
Benign
0.18
Sift
Uncertain
0.012
D;.;T;.
Sift4G
Uncertain
0.013
D;D;D;D
Polyphen
0.98
.;D;D;.
Vest4
0.15
MutPred
0.35
.;Loss of ubiquitination at K295 (P = 0.1);Loss of ubiquitination at K295 (P = 0.1);.;
MVP
0.43
MPC
0.11
ClinPred
0.83
D
GERP RS
4.3
Varity_R
0.13
gMVP
0.12

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: chr19-44739454; API