NM_001351411.2:c.71G>C

Variant names:

• chr9-110942143-C-G
• rs1386066658
• NM_001351411.2:c.71G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001351411.2(LPAR1):​c.71G>C​(p.Cys24Ser) 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: LPAR1 NM_001351411.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

LPAR1 (HGNC:3166): (lysophosphatidic acid receptor 1) The integral membrane protein encoded by this gene is a lysophosphatidic acid (LPA) receptor from a group known as EDG receptors. These receptors are members of the G protein-coupled receptor superfamily. Utilized by LPA for cell signaling, EDG receptors mediate diverse biologic functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. Many transcript variants encoding a few different isoforms have been identified for this gene. [provided by RefSeq, Oct 2020]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351411.2. 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
	LPAR1	NM_001351411.2	MANE Select	c.71G>C	p.Cys24Ser	missense	Exon 5 of 6	NP_001338340.1	Q92633-1
	LPAR1	NM_001351397.2		c.71G>C	p.Cys24Ser	missense	Exon 4 of 5	NP_001338326.1	Q92633-1
	LPAR1	NM_001351398.2		c.71G>C	p.Cys24Ser	missense	Exon 6 of 7	NP_001338327.1	Q92633-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR1	ENST00000683809.1	MANE Select	c.71G>C	p.Cys24Ser	missense	Exon 5 of 6	ENSP00000506912.1	Q92633-1
	LPAR1	ENST00000374430.6	TSL:1	c.71G>C	p.Cys24Ser	missense	Exon 4 of 5	ENSP00000363552.1	Q92633-1
	LPAR1	ENST00000374431.7	TSL:1	c.71G>C	p.Cys24Ser	missense	Exon 4 of 5	ENSP00000363553.3	Q92633-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249942 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

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	1.0
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.87
Sift	Benign	0.060	T
Sift4G	Benign	0.086	T
Polyphen		1.0	D
Vest4		0.91
MVP		0.88
MPC		1.2
ClinPred		0.69	D
GERP RS		5.6
Varity_R		0.50
gMVP		0.95
Mutation Taster		=6/94	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs1386066658; hg19: chr9-113704423;