chr15-34365080-T-C

Position:

• chr15-34365080-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153613.3(LPCAT4):​c.406A>G​(p.Ile136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 2.20

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29113585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPCAT4	NM_153613.3	c.406A>G	p.Ile136Val	missense_variant	3/14	ENST00000314891.11	NP_705841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPCAT4	ENST00000314891.11	c.406A>G	p.Ile136Val	missense_variant	3/14	1	NM_153613.3	ENSP00000317300	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.406A>G (p.I136V) alteration is located in exon 3 (coding exon 3) of the LPCAT4 gene. This alteration results from a A to G substitution at nucleotide position 406, causing the isoleucine (I) at amino acid position 136 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	Benign	0.12
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.010
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Benign	0.040	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.035	D
Polyphen		0.28	B
Vest4		0.31
MutPred		0.50		Loss of catalytic residue at V137 (P = 0.1149);
MVP		0.45
MPC		1.5
ClinPred		0.64	D
GERP RS		5.7
Varity_R		0.19
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs775742765; hg19: chr15-34657281;