Variant 12-6620644-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000329858.9(LPAR5):c.605T>A(p.Leu202Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,402,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LPAR5
ENST00000329858.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

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:

LPAR5 (HGNC:):

LPAR5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPAR5	NM_020400.6 linkuse as main transcript	c.605T>A	p.Leu202Gln	missense_variant	2/2	ENST00000329858.9	NP_065133.1	Q9H1C0Q5KU18
LPAR5	NM_001142961.1 linkuse as main transcript	c.605T>A	p.Leu202Gln	missense_variant	2/2		NP_001136433.1	Q9H1C0Q5KU18
LOC105369631	XR_007063192.1 linkuse as main transcript	n.658+2855A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LPAR5	ENST00000329858.9 linkuse as main transcript	c.605T>A	p.Leu202Gln	missense_variant	2/2	1	NM_020400.6	ENSP00000327875.4	Q9H1C0
LPAR5	ENST00000431922.1 linkuse as main transcript	c.605T>A	p.Leu202Gln	missense_variant	2/2	2		ENSP00000393098.1	Q9H1C0
LPAR5	ENST00000540335.1 linkuse as main transcript	n.962T>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1402662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692616

show subpopulations

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:

9.24e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 13, 2024

The c.605T>A (p.L202Q) alteration is located in exon 2 (coding exon 1) of the LPAR5 gene. This alteration results from a T to A substitution at nucleotide position 605, causing the leucine (L) at amino acid position 202 to be replaced by a glutamine (Q). 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

0.76

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;T

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

T;.

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Uncertain

-0.047

MutationAssessor

Pathogenic

3.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-4.3

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.73

MutPred

0.69

Gain of catalytic residue at L202 (P = 0.0366);Gain of catalytic residue at L202 (P = 0.0366);

MVP

0.67

MPC

1.5

ClinPred

0.99

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.48

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over