chr12-6620790-G-T

Variant names:

• chr12-6620790-G-T
• rs3741924
• NM_020400.6:c.459C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020400.6(LPAR5):​c.459C>A​(p.Ala153Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LPAR5 NM_020400.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 2 publications found

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]

ENSG00000301109 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.658 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR5	NM_020400.6	c.459C>A	p.Ala153Ala	synonymous_variant	Exon 2 of 2	ENST00000329858.9	NP_065133.1
LPAR5	NM_001142961.1	c.459C>A	p.Ala153Ala	synonymous_variant	Exon 2 of 2		NP_001136433.1
LOC105369631	XR_007063192.1	n.658+3001G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPAR5	ENST00000329858.9	c.459C>A	p.Ala153Ala	synonymous_variant	Exon 2 of 2	1	NM_020400.6	ENSP00000327875.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428118 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707800

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32814

American (AMR) AF: 0.00 AC: 0 AN: 40042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25208

East Asian (EAS) AF: 0.00 AC: 0 AN: 38566

South Asian (SAS) AF: 0.00 AC: 0 AN: 82674

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095902

Other (OTH) AF: 0.00 AC: 0 AN: 58972

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.9
DANN	Benign	0.88
PhyloP100		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3741924; hg19: chr12-6729956;