15-34359302-C-T

Variant names:

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

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>A​(p.Cys467Tyr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,350,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/26 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. C467S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: LPCAT4 NM_153613.3 missense, splice_region
• Scores: Splicing: ADA: 0.007343
• Clinical Significance: Not reported in ClinVar
• 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=0.15672094).

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>A	p.Cys467Tyr	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>A	p.Cys467Tyr	missense splice_region	Exon 14 of 14	ENSP00000317300.6	Q643R3
	LPCAT4	ENST00000927810.1		c.1397G>A	p.Cys466Tyr	missense splice_region	Exon 14 of 14	ENSP00000597869.1
	LPCAT4	ENST00000954576.1		c.1391G>A	p.Cys464Tyr	missense splice_region	Exon 14 of 14	ENSP00000624635.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.41e-7 AC: 1 AN: 1350038 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 662744

African (AFR) AF: 0.00 AC: 0 AN: 29406

American (AMR) AF: 0.00 AC: 0 AN: 25252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21606

East Asian (EAS) AF: 0.00 AC: 0 AN: 35096

South Asian (SAS) AF: 0.00 AC: 0 AN: 70644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5414

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1058916

Other (OTH) AF: 0.00 AC: 0 AN: 55816

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.18
Sift	Benign	0.066	T
Sift4G	Benign	0.22	T
Polyphen		0.26	B
Vest4		0.17
MutPred		0.43		Loss of catalytic residue at C467 (P = 0.0428)
MVP		0.17
MPC		0.012
ClinPred		0.30	T
GERP RS		2.2
Varity_R		0.055
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0073
dbscSNV1_RF	Benign	0.19
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		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;