rs147677557

Variant summary

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

The NM_182490.3(ZNF227):​c.299C>G​(p.Thr100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T100I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

ZNF227
NM_182490.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.492
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=0.10331565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF227NM_182490.3 linkc.299C>G p.Thr100Arg 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.299C>G p.Thr100Arg missense_variant Exon 6 of 6 1 NM_182490.3 ENSP00000321049.6 Q86WZ6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.92e-7
AC:
1
AN:
1444944
Hom.:
0
Cov.:
30
AF XY:
0.00000139
AC XY:
1
AN XY:
718498
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:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
7.8
DANN
Benign
0.96
DEOGEN2
Benign
0.21
.;T;.;T;T;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.42
T;T;T;.;T;.
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.10
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
.;M;.;M;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-2.3
N;.;.;D;.;.
REVEL
Benign
0.054
Sift
Benign
0.043
D;.;.;D;.;.
Sift4G
Benign
0.28
T;T;D;T;D;T
Polyphen
0.77
.;P;.;P;.;.
Vest4
0.19
MutPred
0.29
.;Gain of MoRF binding (P = 0.0201);.;Gain of MoRF binding (P = 0.0201);.;.;
MVP
0.17
MPC
0.23
ClinPred
0.15
T
GERP RS
-0.94
Varity_R
0.17
gMVP
0.33

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.

Other links and lift over

dbSNP: rs147677557; hg19: chr19-44738882; API