NM_153613.3:c.490T>C

Variant names:

• chr15-34364295-A-G
• rs1474866665
• NM_153613.3:c.490T>C

Variant summary

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

The NM_153613.3(LPCAT4):​c.490T>C​(p.Phe164Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: LPCAT4 NM_153613.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.46
• Publications: 0 publications found

Genes affected

LPCAT4 (HGNC:30059): (lysophosphatidylcholine acyltransferase 4) Members of the 1-acylglycerol-3-phosphate O-acyltransferase (EC 2.3.1.51) family, such as AGPAT7, catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), a precursor in the biosynthesis of all glycerolipids. Both LPA and PA are involved in signal transduction (Ye et al., 2005 [PubMed 16243729]).[supplied by OMIM, May 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153613.3. 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
	LPCAT4	NM_153613.3	MANE Select	c.490T>C	p.Phe164Leu	missense	Exon 4 of 14	NP_705841.2	Q643R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT4	ENST00000314891.11	TSL:1 MANE Select	c.490T>C	p.Phe164Leu	missense	Exon 4 of 14	ENSP00000317300.6	Q643R3
	LPCAT4	ENST00000566581.5	TSL:1	n.566T>C		non_coding_transcript_exon	Exon 4 of 4
	LPCAT4	ENST00000927810.1		c.490T>C	p.Phe164Leu	missense	Exon 4 of 14	ENSP00000597869.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460366 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726576

African (AFR) AF: 0.0000299 AC: 1 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1110762

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	0.10	N
PhyloP100		6.5
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.72
Sift	Benign	0.61	T
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.42		Loss of methylation at R163 (P = 0.0995)
MVP		0.84
MPC		1.7
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.73
Mutation Taster		=45/55	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

dbSNP: rs1474866665; hg19: chr15-34656496;