Genetic Variant NM_012152.3:c.862G>A (chr1-84814046-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012152.3(LPAR3):c.862G>A(p.Val288Met) variant causes a missense change. The variant allele was found at a frequency of 0.00217 in 1,614,082 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 44 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 23 hom. )

Consequence

LPAR3
NM_012152.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.18

Publications

4 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051103234).

BP6

Variant 1-84814046-C-T is Benign according to our data. Variant chr1-84814046-C-T is described in ClinVar as Benign. ClinVar VariationId is 780244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1776/152196) while in subpopulation AFR AF = 0.0407 (1691/41522). AF 95% confidence interval is 0.0391. There are 44 homozygotes in GnomAd4. There are 866 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1776 AD gene.

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.862G>A	p.Val288Met	missense	Exon 3 of 3	NP_036284.1	Q9UBY5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LPAR3	ENST00000370611.4	TSL:1 MANE Select	c.862G>A	p.Val288Met	missense	Exon 3 of 3	ENSP00000359643.3	Q9UBY5
LPAR3	ENST00000440886.1	TSL:1	c.862G>A	p.Val288Met	missense	Exon 2 of 2	ENSP00000395389.1	Q9UBY5
LPAR3	ENST00000930963.1		c.862G>A	p.Val288Met	missense	Exon 3 of 3	ENSP00000601022.1

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1774

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00320

AC:

805

AN:

251416

AF XY:

0.00239

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00118

AC:

1731

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

744

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0409

AC:

1369

AN:

33480

American (AMR)

AF:

0.00233

AC:

104

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000647

AC:

AN:

1112004

Other (OTH)

AF:

0.00277

AC:

167

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

102

205

307

410

512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0117

AC:

1776

AN:

152196

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

866

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0407

AC:

1691

AN:

41522

American (AMR)

AF:

0.00412

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000208

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68012

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

165

248

330

413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.0133

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0415

AC:

183

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00394

AC:

478

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.032

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.65

PhyloP100

4.2

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.98

REVEL

Benign

0.083

Sift

Benign

1.0

Sift4G

Benign

0.95

Polyphen

0.0

Vest4

0.22

MVP

0.082

MPC

0.16

ClinPred

0.020

GERP RS

3.4

Varity_R

0.078

gMVP

0.36

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over