rs199824078

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030930.4(UNC93B1):​c.1453G>A​(p.Val485Met) variant causes a missense change. The variant allele was found at a frequency of 0.00273 in 1,258,826 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 17 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

10
6

Clinical Significance

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

Conservation

PhyloP100: 4.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013433933).
BP6
Variant 11-67993705-C-T is Benign according to our data. Variant chr11-67993705-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 470491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67993705-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00261 (397/152330) while in subpopulation AMR AF= 0.00588 (90/15308). AF 95% confidence interval is 0.0049. There are 1 homozygotes in gnomad4. There are 211 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UNC93B1NM_030930.4 linkc.1453G>A p.Val485Met missense_variant Exon 10 of 11 ENST00000227471.7 NP_112192.2 Q9H1C4
UNC93B1XM_011545290.1 linkc.1042G>A p.Val348Met missense_variant Exon 8 of 9 XP_011543592.1
UNC93B1XM_011545291.3 linkc.898G>A p.Val300Met missense_variant Exon 7 of 8 XP_011543593.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UNC93B1ENST00000227471.7 linkc.1453G>A p.Val485Met missense_variant Exon 10 of 11 1 NM_030930.4 ENSP00000227471.3 Q9H1C4
UNC93B1ENST00000525368.1 linkn.460G>A non_coding_transcript_exon_variant Exon 2 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.00260
AC:
396
AN:
152212
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00589
Gnomad ASJ
AF:
0.0115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00517
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0380
Gnomad NFE
AF:
0.00287
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00422
AC:
600
AN:
142166
Hom.:
4
AF XY:
0.00456
AC XY:
347
AN XY:
76140
show subpopulations
Gnomad AFR exome
AF:
0.000281
Gnomad AMR exome
AF:
0.00533
Gnomad ASJ exome
AF:
0.0137
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00568
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00311
Gnomad OTH exome
AF:
0.0106
GnomAD4 exome
AF:
0.00275
AC:
3043
AN:
1106496
Hom.:
17
Cov.:
15
AF XY:
0.00297
AC XY:
1656
AN XY:
558282
show subpopulations
Gnomad4 AFR exome
AF:
0.00146
Gnomad4 AMR exome
AF:
0.00579
Gnomad4 ASJ exome
AF:
0.0138
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00565
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00209
Gnomad4 OTH exome
AF:
0.00473
GnomAD4 genome
AF:
0.00261
AC:
397
AN:
152330
Hom.:
1
Cov.:
33
AF XY:
0.00283
AC XY:
211
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000529
Gnomad4 AMR
AF:
0.00588
Gnomad4 ASJ
AF:
0.0115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00518
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00287
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00534
Hom.:
2
Bravo
AF:
0.00308
ExAC
AF:
0.00150
AC:
145

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
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

UNC93B1: BS2 -

Herpes simplex encephalitis, susceptibility to, 1 Benign:1
Jan 24, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
D
MetaRNN
Benign
0.013
T
MetaSVM
Uncertain
0.054
D
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.70
T
REVEL
Uncertain
0.42
Sift4G
Uncertain
0.0080
D
Polyphen
1.0
D
Vest4
0.51
MVP
0.29
MPC
1.3
ClinPred
0.025
T
GERP RS
5.0
Varity_R
0.26
gMVP
0.87

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.

Other links and lift over

dbSNP: rs199824078; hg19: chr11-67761176; COSMIC: COSV57098606; COSMIC: COSV57098606; API