NM_030930.4(UNC93B1):c.1785G>C (p.Glu595Asp) AND Herpes simplex encephalitis, susceptibility to, 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 12, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001201489.6

Allele description [Variation Report for NM_030930.4(UNC93B1):c.1785G>C (p.Glu595Asp)]

NM_030930.4(UNC93B1):c.1785G>C (p.Glu595Asp)

Gene:

UNC93B1:unc-93 homolog B1, TLR signaling regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_030930.4(UNC93B1):c.1785G>C (p.Glu595Asp)

HGVS:

NC_000011.10:g.67991555C>G
NG_007581.1:g.17569G>C
NM_030930.4:c.1785G>CMANE SELECT
NP_112192.2:p.Glu595Asp
LRG_123:g.17569G>C
NC_000011.9:g.67759026C>G
NM_030930.3:c.1785G>C

Protein change:

E595D

Links:

dbSNP: rs761443098

NCBI 1000 Genomes Browser:

rs761443098

Molecular consequence:

NM_030930.4:c.1785G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Herpes simplex encephalitis, susceptibility to, 1 (IIAE1)
Synonyms:: Herpes simplex encephalitis 1; ENCEPHALOPATHY, ACUTE, INFECTION-INDUCED (HERPES-SPECIFIC), SUSCEPTIBILITY TO, 1
Identifiers:: MONDO: MONDO:0024563; MedGen: C2750180; Orphanet: 1930; OMIM: 610551

Recent activity

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Saccharomyces cerevisiae S288C transcription factor MCM1 (MCM1), partial mRNA
Saccharomyces cerevisiae S288C transcription factor MCM1 (MCM1), partial mRNA
gi|296147162|ref|NM_001182540.1|

Nucleotide
cilia- and flagella-associated protein 65 isoform X4 [Mus musculus]
cilia- and flagella-associated protein 65 isoform X4 [Mus musculus]
gi|568906386|ref|XP_006496055.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001372560	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 12, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002496025	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 16, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001372560

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 12, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002496025

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 16, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001372560.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 595 of the UNC93B1 protein (p.Glu595Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with UNC93B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 933307). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV002496025.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

UNC93B1 NM_030930.3 exon 11 p.Glu595Asp (c.1785G>C): This variant has not been reported in the literature but is present in 0.02% (15/67980) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/11-67991555-C-G?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:933307). This variant amino acid (Aspartate) is present in multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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