Variant 11-67991616-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 11/17 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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. Variant chr11-67991616-G-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UNC93B1	NM_030930.4 linkuse as main transcript	c.1724C>A	p.Pro575His	missense_variant	11/11	ENST00000227471.7
UNC93B1	XM_011545290.1 linkuse as main transcript	c.1313C>A	p.Pro438His	missense_variant	9/9
UNC93B1	XM_011545291.3 linkuse as main transcript	c.1169C>A	p.Pro390His	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7 linkuse as main transcript	c.1724C>A	p.Pro575His	missense_variant	11/11	1	NM_030930.4	P1

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

GnomAD3 exomes

AF:

0.00595

AC:

577

AN:

96914

Hom.:

AF XY:

0.00591

AC XY:

321

AN XY:

54314

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 SAS exome

AF:

0.00182

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

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00568

Gnomad4 ASJ exome

AF:

0.00391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00779

GnomAD4 genome

AF:

0.00591

AC:

899

AN:

152222

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00862

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00917

Gnomad4 OTH

AF:

0.0104

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

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	UNC93B1: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

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

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

MutationTaster

Benign

1.0

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

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