rs1060499915

chr11-67997690-GA-Gchr11-67997690-GA-GAA

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_030930.4(UNC93B1):c.890del(p.Phe297SerfsTer152) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: UNC93B1 NM_030930.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.30

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC93B1	NM_030930.4	c.890del	p.Phe297SerfsTer152	frameshift_variant	7/11	ENST00000227471.7
UNC93B1	XM_011545290.1	c.479del	p.Phe160SerfsTer152	frameshift_variant	5/9
UNC93B1	XM_011545291.3	c.335del	p.Phe112SerfsTer152	frameshift_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7	c.890del	p.Phe297SerfsTer152	frameshift_variant	7/11	1	NM_030930.4	P1
UNC93B1	ENST00000533424.6	n.1384del		non_coding_transcript_exon_variant	6/7	5
UNC93B1	ENST00000622364.4	n.888del		non_coding_transcript_exon_variant	7/7	2
UNC93B1	ENST00000531152.3			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1060499915; hg19: chr11-67765161;