1-84865594-C-A

Variant names:

• chr1-84865594-C-A
• NM_012152.3:c.527G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_012152.3(LPAR3):​c.527G>T​(p.Cys176Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPAR3 NM_012152.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012152.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR3	NM_012152.3	MANE Select	c.527G>T	p.Cys176Phe	missense	Exon 2 of 3	NP_036284.1	Q9UBY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR3	ENST00000370611.4	TSL:1 MANE Select	c.527G>T	p.Cys176Phe	missense	Exon 2 of 3	ENSP00000359643.3	Q9UBY5
	LPAR3	ENST00000440886.1	TSL:1	c.527G>T	p.Cys176Phe	missense	Exon 1 of 2	ENSP00000395389.1	Q9UBY5
	LPAR3	ENST00000930963.1		c.527G>T	p.Cys176Phe	missense	Exon 2 of 3	ENSP00000601022.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-10	D
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.94
MutPred		0.89		Loss of catalytic residue at S178 (P = 0.0699)
MVP		0.90
MPC		0.86
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.97
gMVP		0.94
Mutation Taster		=14/86	disease causing

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

Other links and lift over

hg19: chr1-85331277;