Variant X-78755963-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001278000.3(LPAR4):c.1094T>C(p.Met365Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000733 in 1,091,340 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )

Consequence

LPAR4
NM_001278000.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

LPAR4 (HGNC:4478): (lysophosphatidic acid receptor 4) This gene encodes a member of the lysophosphatidic acid receptor family. It may also be related to the P2Y receptors, a family of receptors that bind purine and pyrimidine nucleotides and are coupled to G proteins. The encoded protein may play a role in monocytic differentiation. [provided by RefSeq, Feb 2009]

LPAR4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09197739).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPAR4	NM_001278000.3 linkuse as main transcript	c.1094T>C	p.Met365Thr	missense_variant	5/5	ENST00000614823.5	NP_001264929.1	Q99677

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPAR4	ENST00000614823.5 linkuse as main transcript	c.1094T>C	p.Met365Thr	missense_variant	5/5	4	NM_001278000.3	ENSP00000478261.1		Q99677
LPAR4	ENST00000435339.3 linkuse as main transcript	c.1094T>C	p.Met365Thr	missense_variant	2/2	1		ENSP00000408205.2		Q99677

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000733

AC:

AN:

1091340

Hom.:

Cov.:

AF XY:

0.00000839

AC XY:

AN XY:

357500

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:

0.00000955

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

Jan 23, 2023

The c.1094T>C (p.M365T) alteration is located in exon 2 (coding exon 1) of the LPAR4 gene. This alteration results from a T to C substitution at nucleotide position 1094, causing the methionine (M) at amino acid position 365 to be replaced by a threonine (T). 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

0.085

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.042

T;T

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.46

T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.59

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.29

.;N

REVEL

Benign

0.10

Sift

Benign

0.21

.;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.19

Gain of phosphorylation at M365 (P = 0.1418);Gain of phosphorylation at M365 (P = 0.1418);

MVP

0.39

MPC

0.40

ClinPred

0.10

GERP RS

5.0

Varity_R

0.24

gMVP

0.54

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