11-67991616-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030930.4(UNC93B1):c.1724C>A(p.Pro575His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00885 in 1,501,360 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. 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. P575Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 68 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.49

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)

UNC93B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065273046).

BP6

Variant 11-67991616-G-T is Benign according to our data. Variant chr11-67991616-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 782777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00591 (899/152222) while in subpopulation NFE AF = 0.00917 (623/67966). AF 95% confidence interval is 0.00857. There are 6 homozygotes in GnomAd4. There are 420 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.1724C>A	p.Pro575His	missense_variant	Exon 11 of 11	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.1313C>A	p.Pro438His	missense_variant	Exon 9 of 9		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.1169C>A	p.Pro390His	missense_variant	Exon 8 of 8		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 link	c.1724C>A	p.Pro575His	missense_variant	Exon 11 of 11	1	NM_030930.4	ENSP00000227471.3		Q9H1C4
UNC93B1	ENST00000525368.1 link	n.*202C>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

900

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00863

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00916

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00595

AC:

577

AN:

96914

AF XY:

0.00591

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00571

Gnomad ASJ exome

AF:

0.00409

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00216

Gnomad NFE exome

AF:

0.00980

Gnomad OTH exome

AF:

0.00984

GnomAD4 exome

AF:

0.00918

AC:

12381

AN:

1349138

Hom.:

Cov.:

AF XY:

0.00891

AC XY:

5922

AN XY:

664906

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

27678

American (AMR)

AF:

0.00568

AC:

172

AN:

30282

Ashkenazi Jewish (ASJ)

AF:

0.00391

AC:

AN:

23548

East Asian (EAS)

AF:

0.00

AC:

AN:

33150

South Asian (SAS)

AF:

0.00173

AC:

130

AN:

75186

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

33204

Middle Eastern (MID)

AF:

0.00736

AC:

AN:

3942

European-Non Finnish (NFE)

AF:

0.0107

AC:

11413

AN:

1065926

Other (OTH)

AF:

0.00779

AC:

438

AN:

56222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

727

1454

2182

2909

3636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00591

AC:

899

AN:

152222

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

41552

American (AMR)

AF:

0.00862

AC:

132

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00917

AC:

623

AN:

67966

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00650

ExAC

AF:

0.00195

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

UNC93B1: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

PhyloP100

1.5

PrimateAI

Pathogenic

0.79

REVEL

Benign

0.022

Sift4G

Uncertain

0.0080

Polyphen

0.70

Vest4

0.20

MVP

0.043

MPC

0.91

ClinPred

0.0090

GERP RS

2.4

Varity_R

0.040

gMVP

0.40

Mutation Taster

=100/0

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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11-67991616-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over