19-48286720-T-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The ENST00000595607.6(ZNF114):āc.1096T>Cā(p.Cys366Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
ZNF114
ENST00000595607.6 missense
ENST00000595607.6 missense
Scores
7
9
3
Clinical Significance
Conservation
PhyloP100: 6.40
Genes affected
ZNF114 (HGNC:12894): (zinc finger protein 114) Enables identical protein binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.942
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF114 | NM_153608.4 | c.1096T>C | p.Cys366Arg | missense_variant | 6/6 | ENST00000595607.6 | NP_705836.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF114 | ENST00000595607.6 | c.1096T>C | p.Cys366Arg | missense_variant | 6/6 | 1 | NM_153608.4 | ENSP00000469998.1 | ||
ZNF114 | ENST00000315849.5 | c.1096T>C | p.Cys366Arg | missense_variant | 5/5 | 2 | ENSP00000318898.1 | |||
ZNF114 | ENST00000600687.5 | c.1096T>C | p.Cys366Arg | missense_variant | 5/5 | 5 | ENSP00000471727.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461486Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727028
GnomAD4 exome
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1
AN:
1461486
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31
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1
AN XY:
727028
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
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Bravo
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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 | Apr 26, 2024 | The c.1096T>C (p.C366R) alteration is located in exon 5 (coding exon 3) of the ZNF114 gene. This alteration results from a T to C substitution at nucleotide position 1096, causing the cysteine (C) at amino acid position 366 to be replaced by an arginine (R). 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
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;T
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D
REVEL
Uncertain
Sift
Pathogenic
.;.;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0215);Gain of MoRF binding (P = 0.0215);Gain of MoRF binding (P = 0.0215);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at