chr9-110941705-A-G

Variant names:

• chr9-110941705-A-G
• NM_001351411.2:c.509T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351411.2(LPAR1):​c.509T>C​(p.Val170Ala) 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 benign outcome for this variant. 14/22 in silico tools predict a benign 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: 9.32
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23972479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR1	NM_001351411.2	c.509T>C	p.Val170Ala	missense_variant	Exon 5 of 6	ENST00000683809.1	NP_001338340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR1	ENST00000683809.1	c.509T>C	p.Val170Ala	missense_variant	Exon 5 of 6		NM_001351411.2	ENSP00000506912.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.509T>C (p.V170A) alteration is located in exon 4 (coding exon 2) of the LPAR1 gene. This alteration results from a T to C substitution at nucleotide position 509, causing the valine (V) at amino acid position 170 to be replaced by an alanine (A). 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	0.15
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.55
DEOGEN2	Benign	0.058	T;T;T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	0.063
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.69	.;.;T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.23	N;N;N;.;.
PhyloP100		9.3
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	1.0	N;N;N;.;N
REVEL	Benign	0.22
Sift	Benign	1.0	T;T;T;.;T
Sift4G	Benign	0.89	T;T;T;T;T
Polyphen		0.0	B;B;B;.;.
Vest4		0.54
MVP		0.32
MPC		1.0
ClinPred		0.75	D
GERP RS		5.5
Varity_R		0.13
gMVP		0.84
Mutation Taster		=18/82	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: chr9-113703985;