1-84865556-C-T

Variant summary

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

The NM_012152.3(LPAR3):​c.565G>A​(p.Val189Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V189F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LPAR3
NM_012152.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.38
Variant links:
Genes affected
LPAR3 (HGNC:14298): (lysophosphatidic acid receptor 3) This gene encodes a member of the G protein-coupled receptor family, as well as the EDG family of proteins. This protein functions as a cellular receptor for lysophosphatidic acid and mediates lysophosphatidic acid-evoked calcium mobilization. This receptor couples predominantly to G(q/11) alpha proteins. [provided by RefSeq, Jul 2008]

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=0.10504502).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LPAR3NM_012152.3 linkc.565G>A p.Val189Ile missense_variant Exon 2 of 3 ENST00000370611.4 NP_036284.1 Q9UBY5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LPAR3ENST00000370611.4 linkc.565G>A p.Val189Ile missense_variant Exon 2 of 3 1 NM_012152.3 ENSP00000359643.3 Q9UBY5
LPAR3ENST00000440886.1 linkc.565G>A p.Val189Ile missense_variant Exon 1 of 2 1 ENSP00000395389.1 Q9UBY5
LPAR3ENST00000491034.1 linkn.457-13G>A intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727244
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
13
DANN
Benign
0.69
DEOGEN2
Benign
0.023
T;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.86
.;D
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.24
N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.050
N;N
REVEL
Benign
0.046
Sift
Benign
0.79
T;T
Sift4G
Benign
0.77
T;T
Polyphen
0.0
B;B
Vest4
0.13
MutPred
0.59
Loss of catalytic residue at V189 (P = 0.0357);Loss of catalytic residue at V189 (P = 0.0357);
MVP
0.10
MPC
0.13
ClinPred
0.13
T
GERP RS
1.6
Varity_R
0.028
gMVP
0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-85331239; COSMIC: COSV65455225; API