19-48286720-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000595607.6(ZNF114):ā€‹c.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

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40
Variant links:
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]

Genome browser will be placed here

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
ZNF114NM_153608.4 linkuse as main transcriptc.1096T>C p.Cys366Arg missense_variant 6/6 ENST00000595607.6 NP_705836.1 Q8NC26-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF114ENST00000595607.6 linkuse as main transcriptc.1096T>C p.Cys366Arg missense_variant 6/61 NM_153608.4 ENSP00000469998.1 Q8NC26-1
ZNF114ENST00000315849.5 linkuse as main transcriptc.1096T>C p.Cys366Arg missense_variant 5/52 ENSP00000318898.1 Q8NC26-1
ZNF114ENST00000600687.5 linkuse as main transcriptc.1096T>C p.Cys366Arg missense_variant 5/55 ENSP00000471727.1 Q8NC26-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461486
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727028
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113

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 26, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.54
D;D;D
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.58
.;.;T
M_CAP
Benign
0.011
T
MetaRNN
Pathogenic
0.94
D;D;D
MetaSVM
Uncertain
0.60
D
MutationAssessor
Pathogenic
4.4
H;H;H
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-12
.;.;D
REVEL
Uncertain
0.54
Sift
Pathogenic
0.0
.;.;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.55
MutPred
0.78
Gain of MoRF binding (P = 0.0215);Gain of MoRF binding (P = 0.0215);Gain of MoRF binding (P = 0.0215);
MVP
0.92
MPC
0.90
ClinPred
1.0
D
GERP RS
2.5
Varity_R
0.82
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs999965221; hg19: chr19-48789977; API