chr11-67991605-C-G

Variant names:

• chr11-67991605-C-G
• rs1332464949
• NM_030930.4:c.1735G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 14/19 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.35
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039890975).

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.1735G>C	p.Gly579Arg	missense	Exon 11 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.1735G>C	p.Gly579Arg	missense	Exon 11 of 11	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000864508.1		c.1774G>C	p.Gly592Arg	missense	Exon 11 of 11	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.1759G>C	p.Gly587Arg	missense	Exon 11 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Herpes simplex encephalitis, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-3.3
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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1332464949; hg19: chr11-67759076;