chr11-67991605-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030930.4(UNC93B1):​c.1735G>C​(p.Gly579Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

UNC93B1
NM_030930.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.35
Variant links:
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=0.039890975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UNC93B1NM_030930.4 linkc.1735G>C p.Gly579Arg missense_variant Exon 11 of 11 ENST00000227471.7 NP_112192.2 Q9H1C4
UNC93B1XM_011545290.1 linkc.1324G>C p.Gly442Arg missense_variant Exon 9 of 9 XP_011543592.1
UNC93B1XM_011545291.3 linkc.1180G>C p.Gly394Arg missense_variant Exon 8 of 8 XP_011543593.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UNC93B1ENST00000227471.7 linkc.1735G>C p.Gly579Arg missense_variant Exon 11 of 11 1 NM_030930.4 ENSP00000227471.3 Q9H1C4
UNC93B1ENST00000525368.1 linkn.*213G>C downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

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
Jul 19, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant has not been reported in the literature in individuals affected with UNC93B1-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 645257). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 579 of the UNC93B1 protein (p.Gly579Arg). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.0060
DANN
Benign
0.75
DEOGEN2
Benign
0.060
T
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.20
N
PrimateAI
Pathogenic
0.80
T
REVEL
Benign
0.0060
Sift4G
Benign
0.067
T
Polyphen
0.0
B
Vest4
0.084
MutPred
0.22
Loss of catalytic residue at P575 (P = 0.0722);
MVP
0.043
MPC
0.58
ClinPred
0.050
T
GERP RS
-9.0
Varity_R
0.066
gMVP
0.20

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: rs1332464949; hg19: chr11-67759076; API