1-84865556-C-T

Variant names:

• chr1-84865556-C-T
• NM_012152.3:c.565G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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]

ACMG classification

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
LPAR3	NM_012152.3	c.565G>A	p.Val189Ile	missense_variant	Exon 2 of 3	ENST00000370611.4	NP_036284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR3	ENST00000370611.4	c.565G>A	p.Val189Ile	missense_variant	Exon 2 of 3	1	NM_012152.3	ENSP00000359643.3
LPAR3	ENST00000440886.1	c.565G>A	p.Val189Ile	missense_variant	Exon 1 of 2	1		ENSP00000395389.1
LPAR3	ENST00000491034.1	n.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

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;