Genetic Variant NM_030930.4:c.1733T>G (chr11-67991607-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030930.4(UNC93B1):c.1733T>G(p.Leu578Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,706 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41

Publications

0 publications found

Variant links:

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

UNC93B1 links:

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ACMG classification

Classification was made for transcript

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=0.05083993).

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.1733T>G	p.Leu578Arg	missense	Exon 11 of 11	NP_112192.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.1733T>G	p.Leu578Arg	missense	Exon 11 of 11	ENSP00000227471.3	Q9H1C4
UNC93B1	ENST00000864508.1		c.1772T>G	p.Leu591Arg	missense	Exon 11 of 11	ENSP00000534567.1
UNC93B1	ENST00000864509.1		c.1757T>G	p.Leu586Arg	missense	Exon 11 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.44e-7

AC:

AN:

1344706

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

662560

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27230

American (AMR)

AF:

0.00

AC:

AN:

29718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23408

East Asian (EAS)

AF:

0.00

AC:

AN:

32744

South Asian (SAS)

AF:

0.00

AC:

AN:

74758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3924

European-Non Finnish (NFE)

AF:

9.40e-7

AC:

AN:

1063766

Other (OTH)

AF:

0.00

AC:

AN:

55968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Herpes simplex encephalitis, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.050

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.052

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.51

M_CAP

Benign

0.013

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.71

PhyloP100

-1.4

PrimateAI

Uncertain

0.77

REVEL

Benign

0.024

Sift4G

Benign

0.81

Polyphen

0.0

Vest4

0.078

MutPred

0.25

Gain of solvent accessibility (P = 1e-04)

MVP

0.043

MPC

0.62

ClinPred

0.015

GERP RS

-2.6

Varity_R

0.054

gMVP

0.25

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over