15-34359302-C-G

Variant names:

• chr15-34359302-C-G
• rs762126781
• NM_153613.3:c.1400G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153613.3(LPCAT4):​c.1400G>C​(p.Cys467Ser) variant causes a missense, splice region 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. 15/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LPCAT4 NM_153613.3 missense, splice_region
• Scores: Splicing: ADA: 0.07788
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11393684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPCAT4	NM_153613.3	c.1400G>C	p.Cys467Ser	missense_variant, splice_region_variant	Exon 14 of 14	ENST00000314891.11	NP_705841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPCAT4	ENST00000314891.11	c.1400G>C	p.Cys467Ser	missense_variant, splice_region_variant	Exon 14 of 14	1	NM_153613.3	ENSP00000317300.6
LPCAT4	ENST00000563748.5	n.964G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	2
LPCAT4	ENST00000567507.1	n.*211G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000454422.1
LPCAT4	ENST00000567507.1	n.*211G>C		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000454422.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000900 AC: 1 AN: 111170 Hom.: 0 AF XY: 0.0000176 AC XY: 1 AN XY: 56866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000222

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000995 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1400G>C (p.C467S) alteration is located in exon 14 (coding exon 14) of the LPCAT4 gene. This alteration results from a G to C substitution at nucleotide position 1400, causing the cysteine (C) at amino acid position 467 to be replaced by a serine (S). 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	0.076
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.72
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.65	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.76	N;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.87	N;.
REVEL	Benign	0.21
Sift	Benign	0.72	T;.
Sift4G	Benign	0.37	T;T
Polyphen		0.0050	B;.
Vest4		0.17
MutPred		0.50		Gain of disorder (P = 0.0014);.;
MVP		0.27
MPC		0.010
ClinPred		0.10	T
GERP RS		2.2
Varity_R		0.040
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.078
dbscSNV1_RF	Benign	0.37
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs762126781; hg19: chr15-34651503;