chr19-44106852-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001321645.3(ZNF224):c.692C>T(p.Pro231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,612,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
ZNF224
NM_001321645.3 missense
NM_001321645.3 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 1.59
Genes affected
ZNF224 (HGNC:13017): (zinc finger protein 224) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein represses transcription of the aldolase A gene, which encodes a key enzyme in glycolysis. The encoded zinc-finger protein may also function as a transcriptional co-activator with Wilms' tumor protein 1 to regulate apoptotic genes in leukemia. [provided by RefSeq, Jul 2016]
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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=0.18908554).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF224 | NM_001321645.3 | c.692C>T | p.Pro231Leu | missense_variant | 6/6 | ENST00000693561.1 | |
ZNF225-AS1 | NR_033341.1 | n.1848G>A | non_coding_transcript_exon_variant | 2/2 | |||
ZNF224 | NM_013398.5 | c.692C>T | p.Pro231Leu | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF224 | ENST00000693561.1 | c.692C>T | p.Pro231Leu | missense_variant | 6/6 | NM_001321645.3 | P1 | ||
ZNF225-AS1 | ENST00000661725.1 | n.1848G>A | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152174Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249918Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135060
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1460592Hom.: 0 Cov.: 88 AF XY: 0.0000193 AC XY: 14AN XY: 726606
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74330
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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 submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.692C>T (p.P231L) alteration is located in exon 6 (coding exon 4) of the ZNF224 gene. This alteration results from a C to T substitution at nucleotide position 692, causing the proline (P) at amino acid position 231 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of disorder (P = 0.0427);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at