NM_001013615.3:c.289C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013615.3(LURAP1):​c.289C>T​(p.Arg97Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LURAP1
NM_001013615.3 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.779
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LURAP1NM_001013615.3 linkc.289C>T p.Arg97Trp missense_variant Exon 2 of 2 ENST00000371980.4 NP_001013633.1 Q96LR2
POMGNT1NM_001243766.2 linkc.-135G>A 5_prime_UTR_variant Exon 1 of 23 NP_001230695.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LURAP1ENST00000371980.4 linkc.289C>T p.Arg97Trp missense_variant Exon 2 of 2 1 NM_001013615.3 ENSP00000361048.3 Q96LR2
POMGNT1ENST00000371992.1 linkc.-135G>A 5_prime_UTR_variant Exon 1 of 23 2 ENSP00000361060.1 Q8WZA1-2
POMGNT1ENST00000693223.1 linkn.514G>A non_coding_transcript_exon_variant Exon 1 of 20

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251200
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461804
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
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
Nov 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.289C>T (p.R97W) alteration is located in exon 2 (coding exon 2) of the LURAP1 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the arginine (R) at amino acid position 97 to be replaced by a tryptophan (W). 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
Uncertain
0.38
BayesDel_addAF
Benign
0.0027
T
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.17
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.48
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Uncertain
0.29
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.58
MutPred
0.30
Gain of catalytic residue at R97 (P = 0.007);
MVP
0.36
MPC
0.83
ClinPred
0.98
D
GERP RS
2.7
Varity_R
0.51
gMVP
0.50

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: rs776263232; hg19: chr1-46685461; API