1-84814008-C-T

Position:

• chr1-84814008-C-T

Variant summary

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

The NM_012152.3(LPAR3):​c.900G>A​(p.Met300Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LPAR3 NM_012152.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88

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]

LPAR3 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
LPAR3	NM_012152.3	c.900G>A	p.Met300Ile	missense_variant	3/3	ENST00000370611.4	NP_036284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPAR3	ENST00000370611.4	c.900G>A	p.Met300Ile	missense_variant	3/3	1	NM_012152.3	ENSP00000359643.3
LPAR3	ENST00000440886.1	c.900G>A	p.Met300Ile	missense_variant	2/2	1		ENSP00000395389.1
LPAR3	ENST00000491034.1	n.779G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

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

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

Nov 09, 2024

The c.900G>A (p.M300I) alteration is located in exon 3 (coding exon 2) of the LPAR3 gene. This alteration results from a G to A substitution at nucleotide position 900, causing the methionine (M) at amino acid position 300 to be replaced by an isoleucine (I). 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	0.95
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.38
Sift	Benign	0.050	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.94	P;P
Vest4		0.68
MutPred		0.66		Gain of catalytic residue at M300 (P = 0.0067);Gain of catalytic residue at M300 (P = 0.0067);
MVP		0.71
MPC		0.71
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.61
gMVP		0.79

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: chr1-85279691;