Variant 12-6620519-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020400.6(LPAR5):c.730C>G(p.Leu244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000007 in 1,428,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

LPAR5
NM_020400.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200

Variant links:

Genes affected

LPAR5 (HGNC:13307): (lysophosphatidic acid receptor 5) This gene encodes a member of the rhodopsin class of G protein-coupled transmembrane receptors. This protein transmits extracellular signals from lysophosphatidic acid to cells through heterotrimeric G proteins and mediates numerous cellular processes. Many G protein receptors serve as targets for pharmaceutical drugs. Transcript variants of this gene have been described.[provided by RefSeq, Dec 2008]

LPAR5 links:

LOC105369631 (HGNC:):

LOC105369631 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18126914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LPAR5	NM_020400.6 linkuse as main transcript	c.730C>G	p.Leu244Val	missense_variant	2/2	ENST00000329858.9	NP_065133.1
LOC105369631	XR_007063192.1 linkuse as main transcript	n.658+2730G>C		intron_variant, non_coding_transcript_variant
LPAR5	NM_001142961.1 linkuse as main transcript	c.730C>G	p.Leu244Val	missense_variant	2/2		NP_001136433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LPAR5	ENST00000329858.9 linkuse as main transcript	c.730C>G	p.Leu244Val	missense_variant	2/2	1	NM_020400.6	ENSP00000327875	P1
LPAR5	ENST00000431922.1 linkuse as main transcript	c.730C>G	p.Leu244Val	missense_variant	2/2	2		ENSP00000393098	P1
LPAR5	ENST00000540335.1 linkuse as main transcript	n.1087C>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000216

AC:

AN:

185494

Hom.:

AF XY:

0.0000197

AC XY:

AN XY:

101648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000143

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000700

AC:

AN:

1428910

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

708140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000153

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:

0.00000365

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.730C>G (p.L244V) alteration is located in exon 2 (coding exon 1) of the LPAR5 gene. This alteration results from a C to G substitution at nucleotide position 730, causing the leucine (L) at amino acid position 244 to be replaced by a valine (V). 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

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.71

T;.

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.56

N;N

MutationTaster

Benign

0.70

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.48

P;P

Vest4

0.13

MutPred

0.55

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MVP

0.76

MPC

0.78

ClinPred

0.080

GERP RS

4.0

Varity_R

0.068

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over