chr12-6981606-C-T

Position:

• chr12-6981606-C-T

Variant summary

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

The NM_005768.6(LPCAT3):​c.487G>A​(p.Gly163Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LPCAT3 NM_005768.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.10

Genes affected

LPCAT3 (HGNC:30244): (lysophosphatidylcholine acyltransferase 3) Enables 1-acylglycerophosphocholine O-acyltransferase activity; 1-acylglycerophosphoethanolamine O-acyltransferase activity; and 1-acylglycerophosphoserine O-acyltransferase activity. Involved in phosphatidylcholine acyl-chain remodeling; phosphatidylethanolamine acyl-chain remodeling; and phosphatidylserine acyl-chain remodeling. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290146 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPCAT3	NM_005768.6	c.487G>A	p.Gly163Arg	missense_variant	5/13	ENST00000261407.9	NP_005759.4
EMG1	NR_135131.2	n.633-6176C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPCAT3	ENST00000261407.9	c.487G>A	p.Gly163Arg	missense_variant	5/13	1	NM_005768.6	ENSP00000261407.4
ENSG00000290146	ENST00000607161.5	n.625-6176C>T		intron_variant		2		ENSP00000480420.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Nov 07, 2024

The c.487G>A (p.G163R) alteration is located in exon 5 (coding exon 5) of the LPCAT3 gene. This alteration results from a G to A substitution at nucleotide position 487, causing the glycine (G) at amino acid position 163 to be replaced by an arginine (R). 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	0.26
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.0094	T
Eigen	Benign	0.089
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.36	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.25
Sift	Benign	0.84	T
Sift4G	Benign	0.81	T
Polyphen		0.41	B
Vest4		0.76
MutPred		0.41		Gain of solvent accessibility (P = 0.0306);
MVP		0.73
MPC		1.4
ClinPred		0.75	D
GERP RS		5.3
Varity_R		0.11
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-7090767;