1-46203559-C-T

Variant summary

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

The NM_001013615.3(LURAP1):​c.133C>T​(p.Leu45Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000319 in 1,566,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LURAP1
NM_001013615.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93
Variant links:
Genes affected
LURAP1 (HGNC:32327): (leucine rich adaptor protein 1) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of cytokine production. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]
POMGNT1 (HGNC:19139): (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)) This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

Genome browser will be placed here

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=0.14591688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LURAP1NM_001013615.3 linkc.133C>T p.Leu45Phe missense_variant Exon 1 of 2 ENST00000371980.4 NP_001013633.1 Q96LR2
POMGNT1NM_001243766.2 linkc.-50-5688G>A intron_variant Intron 1 of 22 NP_001230695.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LURAP1ENST00000371980.4 linkc.133C>T p.Leu45Phe missense_variant Exon 1 of 2 1 NM_001013615.3 ENSP00000361048.3 Q96LR2
POMGNT1ENST00000371992.1 linkc.-50-5688G>A intron_variant Intron 1 of 22 2 ENSP00000361060.1 Q8WZA1-2
POMGNT1ENST00000693223.1 linkn.599-5688G>A intron_variant Intron 1 of 19

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152116
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000500
AC:
1
AN:
199810
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
108466
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000387
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000141
AC:
2
AN:
1414432
Hom.:
0
Cov.:
30
AF XY:
0.00000142
AC XY:
1
AN XY:
701968
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000559
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152234
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.133C>T (p.L45F) alteration is located in exon 1 (coding exon 1) of the LURAP1 gene. This alteration results from a C to T substitution at nucleotide position 133, causing the leucine (L) at amino acid position 45 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.53
N
REVEL
Benign
0.20
Sift
Benign
0.32
T
Sift4G
Uncertain
0.059
T
Polyphen
0.94
P
Vest4
0.23
MVP
0.56
MPC
0.63
ClinPred
0.81
D
GERP RS
4.9
Varity_R
0.090
gMVP
0.048

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs199661717; hg19: chr1-46669231; API