11-58617326-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_053023.5(ZFP91):c.1333G>A(p.Val445Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,088 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 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
ZFP91
NM_053023.5 missense
NM_053023.5 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
ZFP91 (HGNC:14983): (ZFP91 zinc finger protein, atypical E3 ubiquitin ligase) The protein encoded by this gene is a member of the zinc finger family of proteins. The gene product contains C2H2-type domains, which are the classical zinc finger domains found in numerous nucleic acid-binding proteins. This protein functions as a regulator of the non-canonical NF-kappaB pathway in lymphotoxin-beta receptor signaling. Alternative splicing results in multiple transcript variants. A read-through transcript variant composed of ZFP91 and the downstream CNTF gene sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. A ZFP91-related pseudogene has also been identified on chromosome 2. [provided by RefSeq, Oct 2010]
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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=0.24553564).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFP91 | NM_053023.5 | c.1333G>A | p.Val445Ile | missense_variant | 11/11 | ENST00000316059.7 | |
ZFP91-CNTF | NR_024091.1 | n.1501G>A | non_coding_transcript_exon_variant | 11/13 | |||
ZFP91 | NM_001197051.2 | c.1330G>A | p.Val444Ile | missense_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFP91 | ENST00000316059.7 | c.1333G>A | p.Val445Ile | missense_variant | 11/11 | 1 | NM_053023.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248186Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134314
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461768Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 727172
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74482
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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 | Jun 06, 2023 | The c.1333G>A (p.V445I) alteration is located in exon 11 (coding exon 11) of the ZFP91 gene. This alteration results from a G to A substitution at nucleotide position 1333, causing the valine (V) at amino acid position 445 to be replaced by an isoleucine (I). 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
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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