chr19-22391944-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001098626.2(ZNF98):c.1291G>A(p.Glu431Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00010 ( 0 hom., cov: 20)
Exomes 𝑓: 0.00011 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ZNF98
NM_001098626.2 missense
NM_001098626.2 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 1.20
Genes affected
ZNF98 (HGNC:13174): (zinc finger protein 98) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.031885087).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF98 | NM_001098626.2 | c.1291G>A | p.Glu431Lys | missense_variant | 4/4 | ENST00000357774.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF98 | ENST00000357774.9 | c.1291G>A | p.Glu431Lys | missense_variant | 4/4 | 1 | NM_001098626.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 14AN: 134208Hom.: 0 Cov.: 20 FAILED QC
GnomAD3 genomes
?
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20
FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000110 AC: 155AN: 1411760Hom.: 0 Cov.: 33 AF XY: 0.000117 AC XY: 82AN XY: 699884
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000104 AC: 14AN: 134330Hom.: 0 Cov.: 20 AF XY: 0.0000464 AC XY: 3AN XY: 64610
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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 | Feb 27, 2023 | The c.1291G>A (p.E431K) alteration is located in exon 4 (coding exon 4) of the ZNF98 gene. This alteration results from a G to A substitution at nucleotide position 1291, causing the glutamic acid (E) at amino acid position 431 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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
Benign
L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of methylation at E431 (P = 0.0098);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at