15-34360152-C-T

Variant names:

• chr15-34360152-C-T
• rs866613649
• NM_153613.3:c.1201G>A

Variant summary

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

The NM_153613.3(LPCAT4):​c.1201G>A​(p.Gly401Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G401W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LPCAT4 NM_153613.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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=0.09462136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPCAT4	NM_153613.3	c.1201G>A	p.Gly401Arg	missense_variant	Exon 12 of 14	ENST00000314891.11	NP_705841.2
LPCAT4	XM_047432334.1	c.1262G>A	p.Trp421*	stop_gained	Exon 13 of 14		XP_047288290.1
LPCAT4	XM_006720454.2	c.*106G>A		3_prime_UTR_variant	Exon 14 of 14		XP_006720517.1
LPCAT4	XR_007064436.1	n.1164G>A		non_coding_transcript_exon_variant	Exon 11 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPCAT4	ENST00000314891.11	c.1201G>A	p.Gly401Arg	missense_variant	Exon 12 of 14	1	NM_153613.3	ENSP00000317300.6
LPCAT4	ENST00000563748.5	n.400G>A		non_coding_transcript_exon_variant	Exon 4 of 5	2
LPCAT4	ENST00000567507.1	n.*12G>A		non_coding_transcript_exon_variant	Exon 3 of 5	3		ENSP00000454422.1
LPCAT4	ENST00000567507.1	n.*12G>A		3_prime_UTR_variant	Exon 3 of 5	3		ENSP00000454422.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.79	N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.52	N;.
REVEL	Benign	0.062
Sift	Benign	0.17	T;.
Sift4G	Benign	0.68	T;T
Polyphen		0.014	B;.
Vest4		0.20
MutPred		0.36		Gain of solvent accessibility (P = 0.019);.;
MVP		0.23
MPC		0.82
ClinPred		0.77	D
GERP RS		3.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.042
gMVP		0.43

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: rs866613649; hg19: chr15-34652353;