9-110942155-T-A

Variant names:

• chr9-110942155-T-A
• rs757912248
• NM_001351411.2:c.59A>T

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.59A>T​(p.Asn20Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N20S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LPAR1 NM_001351411.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• 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=0.22343251).

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.59A>T	p.Asn20Ile	missense	Exon 5 of 6	NP_001338340.1	Q92633-1
	LPAR1	NM_001351397.2		c.59A>T	p.Asn20Ile	missense	Exon 4 of 5	NP_001338326.1	Q92633-1
	LPAR1	NM_001351398.2		c.59A>T	p.Asn20Ile	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.59A>T	p.Asn20Ile	missense	Exon 5 of 6	ENSP00000506912.1	Q92633-1
	LPAR1	ENST00000374430.6	TSL:1	c.59A>T	p.Asn20Ile	missense	Exon 4 of 5	ENSP00000363552.1	Q92633-1
	LPAR1	ENST00000374431.7	TSL:1	c.59A>T	p.Asn20Ile	missense	Exon 4 of 5	ENSP00000363553.3	Q92633-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457134 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724506

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 85022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110292

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.023
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.24
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.039	D
Polyphen		0.0030	B
Vest4		0.29
MVP		0.75
MPC		0.95
ClinPred		0.46	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.76
Mutation Taster		=81/19	polymorphism

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

dbSNP: rs757912248; hg19: chr9-113704435;