9-12775896-A-C

Variant summary

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

The ENST00000319264.4(LURAP1L):ā€‹c.181A>Cā€‹(p.Ser61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S61C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LURAP1L
ENST00000319264.4 missense

Scores

3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66
Variant links:
Genes affected
LURAP1L (HGNC:31452): (leucine rich adaptor protein 1 like) Predicted to be involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. [provided by Alliance of Genome Resources, Apr 2022]
LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

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=0.17296797).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LURAP1LNM_203403.2 linkuse as main transcriptc.181A>C p.Ser61Arg missense_variant 1/2 ENST00000319264.4 NP_981948.1
LURAP1L-AS1NR_125775.1 linkuse as main transcriptn.243+14724T>G intron_variant, non_coding_transcript_variant
LURAP1LXM_005251443.4 linkuse as main transcriptc.181A>C p.Ser61Arg missense_variant 1/2 XP_005251500.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LURAP1LENST00000319264.4 linkuse as main transcriptc.181A>C p.Ser61Arg missense_variant 1/21 NM_203403.2 ENSP00000321026 P1
LURAP1L-AS1ENST00000417638.1 linkuse as main transcriptn.199+14724T>G intron_variant, non_coding_transcript_variant 3
LURAP1LENST00000489107.1 linkuse as main transcriptn.229A>C non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000213
AC:
3
AN:
1408614
Hom.:
0
Cov.:
33
AF XY:
0.00000287
AC XY:
2
AN XY:
697756
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000277
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 09, 2021The c.181A>C (p.S61R) alteration is located in exon 1 (coding exon 1) of the LURAP1L gene. This alteration results from a A to C substitution at nucleotide position 181, causing the serine (S) at amino acid position 61 to be replaced by an arginine (R). 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
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
15
DANN
Uncertain
1.0
Eigen
Benign
0.0012
Eigen_PC
Benign
0.069
FATHMM_MKL
Benign
0.76
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
0.92
D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.54
N
REVEL
Benign
0.12
Sift
Benign
0.45
T
Sift4G
Uncertain
0.025
D
Vest4
0.36
MVP
0.64
MPC
0.15
ClinPred
0.32
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.28

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: rs952142933; hg19: chr9-12775895; API