11-67991615-GG-CT

Position:

• chr11-67991615-GG-CT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_030930.4(UNC93B1):​c.1724_1725delinsAG​(p.Pro575Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P575H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UNC93B1 NM_030930.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.49

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-67991615-GG-CT is Benign according to our data. Variant chr11-67991615-GG-CT is described in ClinVar as [Likely_benign]. Clinvar id is 470494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC93B1	NM_030930.4	c.1724_1725delinsAG	p.Pro575Gln	missense_variant	11/11	ENST00000227471.7	NP_112192.2
UNC93B1	XM_011545290.1	c.1313_1314delinsAG	p.Pro438Gln	missense_variant	9/9		XP_011543592.1
UNC93B1	XM_011545291.3	c.1169_1170delinsAG	p.Pro390Gln	missense_variant	8/8		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1724_1725delinsAG	p.Pro575Gln	missense_variant	11/11	1	NM_030930.4	ENSP00000227471	P1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 15, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554984685; hg19: chr11-67759086; COSMIC: COSV57100447;