rs543443741
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_030930.4(UNC93B1):c.1594C>A(p.Pro532Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,538,928 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 0.00011 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
UNC93B1
NM_030930.4 missense
NM_030930.4 missense
Scores
4
5
8
Clinical Significance
Conservation
PhyloP100: 8.93
Genes affected
UNC93B1 (HGNC:13481): (unc-93 homolog B1, TLR signaling regulator) This gene encodes a protein that is involved in innate and adaptive immune response by regulating toll-like receptor signaling. The encoded protein traffics nucleotide sensing toll-like receptors to the endolysosome from the endoplasmic reticulum. Deficiency of the encoded protein has been associated with herpes simplex encephalitis. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028241515).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UNC93B1 | NM_030930.4 | c.1594C>A | p.Pro532Thr | missense_variant | 11/11 | ENST00000227471.7 | NP_112192.2 | |
UNC93B1 | XM_011545290.1 | c.1183C>A | p.Pro395Thr | missense_variant | 9/9 | XP_011543592.1 | ||
UNC93B1 | XM_011545291.3 | c.1039C>A | p.Pro347Thr | missense_variant | 8/8 | XP_011543593.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UNC93B1 | ENST00000227471.7 | c.1594C>A | p.Pro532Thr | missense_variant | 11/11 | 1 | NM_030930.4 | ENSP00000227471 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152190Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000240 AC: 31AN: 129112Hom.: 0 AF XY: 0.000284 AC XY: 20AN XY: 70538
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GnomAD4 exome AF: 0.000112 AC: 155AN: 1386620Hom.: 0 Cov.: 32 AF XY: 0.000130 AC XY: 89AN XY: 685002
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152308Hom.: 0 Cov.: 34 AF XY: 0.000107 AC XY: 8AN XY: 74474
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 12, 2022 | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 532 of the UNC93B1 protein (p.Pro532Thr). This variant is present in population databases (rs543443741, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with UNC93B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 470492). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
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
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
REVEL
Benign
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of phosphorylation at P532 (P = 0.0047);
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