NM_153613.3:c.598T>G

Variant names:

• chr15-34364067-A-C
• NM_153613.3:c.598T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153613.3(LPCAT4):​c.598T>G​(p.Phe200Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPCAT4 NM_153613.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPCAT4	NM_153613.3	c.598T>G	p.Phe200Val	missense_variant	Exon 5 of 14	ENST00000314891.11	NP_705841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPCAT4	ENST00000314891.11	c.598T>G	p.Phe200Val	missense_variant	Exon 5 of 14	1	NM_153613.3	ENSP00000317300.6
LPCAT4	ENST00000566581.5	n.794T>G		non_coding_transcript_exon_variant	Exon 4 of 4	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 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.598T>G (p.F200V) alteration is located in exon 5 (coding exon 5) of the LPCAT4 gene. This alteration results from a T to G substitution at nucleotide position 598, causing the phenylalanine (F) at amino acid position 200 to be replaced by a valine (V). 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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.56	T;D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Uncertain	0.079	D
MutationAssessor	Benign	-0.45	N;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.82	N;.
REVEL	Uncertain	0.58
Sift	Benign	0.88	T;.
Sift4G	Benign	0.71	T;T
Polyphen		0.91	P;.
Vest4		0.54
MutPred		0.49		Loss of stability (P = 0.0805);.;
MVP		0.69
MPC		1.6
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.23
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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.

Other links and lift over

hg19: chr15-34656268;