UNC93B1 p.Glu45Asp

Variant names:

• chr11-68003760-C-A
• NM_030930.4:c.135G>T
• UNC93B1 p.Glu45Asp

Your query was ambiguous. Multiple possible variants found:

• chr11-68003760-C-A
• chr11-68003760-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030930.4(UNC93B1):​c.135G>T​(p.Glu45Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E45Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UNC93B1 NM_030930.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

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]

UNC93B1 Gene-Disease associations (from GenCC):

• herpes simplex encephalitis, susceptibility to, 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• systemic lupus erythematosus

  Inheritance: SD Classification: MODERATE Submitted by: ClinGen

ENSG00000309414 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3283957).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030930.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	NM_030930.4	MANE Select	c.135G>T	p.Glu45Asp	missense	Exon 2 of 11	NP_112192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.135G>T	p.Glu45Asp	missense	Exon 2 of 11	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000528423.1	TSL:3	c.-79G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000437195.1	E9PNE5
	UNC93B1	ENST00000864508.1		c.174G>T	p.Glu58Asp	missense	Exon 2 of 11	ENSP00000534567.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1369006 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 675602

African (AFR) AF: 0.00 AC: 0 AN: 28996

American (AMR) AF: 0.00 AC: 0 AN: 34540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24676

East Asian (EAS) AF: 0.00 AC: 0 AN: 33608

South Asian (SAS) AF: 0.00 AC: 0 AN: 77208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072926

Other (OTH) AF: 0.00 AC: 0 AN: 57216

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.10
Sift	Benign	0.28	T
Sift4G	Pathogenic	0.0	D
PromoterAI		-0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.48
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-67771230;