rs762126781

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-34359302-C-G
• chr15-34359302-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/26 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
• 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 0 ACMG points.

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

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.1400G>C	p.Cys467Ser	missense splice_region	Exon 14 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.1400G>C	p.Cys467Ser	missense splice_region	Exon 14 of 14	ENSP00000317300.6	Q643R3
	LPCAT4	ENST00000927810.1		c.1397G>C	p.Cys466Ser	missense splice_region	Exon 14 of 14	ENSP00000597869.1
	LPCAT4	ENST00000954576.1		c.1391G>C	p.Cys464Ser	missense splice_region	Exon 14 of 14	ENSP00000624635.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000900 AC: 1 AN: 111170 AF XY: 0.0000176

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 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

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	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
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.76	N
PhyloP100		1.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.87	N
REVEL	Benign	0.21
Sift	Benign	0.72	T
Sift4G	Benign	0.37	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

Other links and lift over

dbSNP: rs762126781; hg19: chr15-34651503;