Variant 11-67991598-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030930.4(UNC93B1):c.1742G>T(p.Arg581Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000669 in 1,344,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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: 0.0000067 ( 0 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12046838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UNC93B1	NM_030930.4 linkuse as main transcript	c.1742G>T	p.Arg581Leu	missense_variant	11/11	ENST00000227471.7
UNC93B1	XM_011545290.1 linkuse as main transcript	c.1331G>T	p.Arg444Leu	missense_variant	9/9
UNC93B1	XM_011545291.3 linkuse as main transcript	c.1187G>T	p.Arg396Leu	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7 linkuse as main transcript	c.1742G>T	p.Arg581Leu	missense_variant	11/11	1	NM_030930.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

94000

Hom.:

AF XY:

0.0000568

AC XY:

AN XY:

52790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000150

Gnomad SAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000669

AC:

AN:

1344968

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

662476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000305

Gnomad4 SAS exome

AF:

0.000107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000794

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2020

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with UNC93B1-related conditions. While this variant is present in population databases (rs754871549), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces arginine with leucine at codon 581 of the UNC93B1 protein (p.Arg581Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.80

M_CAP

Benign

0.049

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

REVEL

Benign

0.023

Sift4G

Uncertain

0.016

Polyphen

0.18

Vest4

0.24

MutPred

0.24

Loss of helix (P = 0.1299);

MVP

0.043

MPC

0.72

ClinPred

0.22

GERP RS

3.6

Varity_R

0.075

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over