1-84865499-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_012152.3(LPAR3):c.622C>G(p.Arg208Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R208Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: LPAR3 NM_012152.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.972

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 Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911
• BS2: High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPAR3	NM_012152.3	c.622C>G	p.Arg208Gly	missense_variant	2/3	ENST00000370611.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPAR3	ENST00000370611.4	c.622C>G	p.Arg208Gly	missense_variant	2/3	1	NM_012152.3	P1
LPAR3	ENST00000440886.1	c.622C>G	p.Arg208Gly	missense_variant	1/2	1		P1
LPAR3	ENST00000491034.1	n.501C>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251296 Hom.: 1 AF XY: 0.0000295 AC XY: 4 AN XY: 135810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 35 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 727242

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: 0.0000315

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2023

The c.622C>G (p.R208G) alteration is located in exon 2 (coding exon 1) of the LPAR3 gene. This alteration results from a C to G substitution at nucleotide position 622, causing the arginine (R) at amino acid position 208 to be replaced by a glycine (G). 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	0.10
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.073	T;T
Polyphen		1.0	D;D
Vest4		0.89
MutPred		0.73		Loss of MoRF binding (P = 0.0048);Loss of MoRF binding (P = 0.0048);
MVP		0.71
MPC		0.78
ClinPred		0.90	D
GERP RS		1.9
Varity_R		0.83
gMVP		0.88

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

Other links and lift over

dbSNP: rs376417362; hg19: chr1-85331182;