NM_005768.6:c.1033G>A

Variant names:

• chr12-6978348-C-T
• rs372779694
• NM_005768.6:c.1033G>A

Variant summary

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

The NM_005768.6(LPCAT3):​c.1033G>A​(p.Val345Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,828 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LPCAT3 NM_005768.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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]

EMG1 (HGNC:16912): (EMG1 N1-specific pseudouridine methyltransferase) This gene encodes an essential, conserved eukaryotic protein that methylates pseudouridine in 18S rRNA. The related protein in yeast is a component of the small subunit processome and is essential for biogenesis of the ribosomal 40S subunit. A mutation in this gene has been associated with Bowen-Conradi syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

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 rank	MANE	Protein	UniProt
LPCAT3	NM_005768.6	c.1033G>A	p.Val345Met	missense_variant	Exon 9 of 13	ENST00000261407.9	NP_005759.4
EMG1	NM_006331.8	c.*2539C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000599672.6	NP_006322.4
EMG1	NM_001320049.2	c.*2539C>T		3_prime_UTR_variant	Exon 5 of 5		NP_001306978.1
EMG1	NR_135131.2	n.632+2970C>T		intron_variant	Intron 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPCAT3	ENST00000261407.9	c.1033G>A	p.Val345Met	missense_variant	Exon 9 of 13	1	NM_005768.6	ENSP00000261407.4
EMG1	ENST00000599672.6	c.*2539C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_006331.8	ENSP00000470560.1
ENSG00000290146	ENST00000607161.5	n.624+2970C>T		intron_variant	Intron 5 of 7	2		ENSP00000480420.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456828 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724198

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.: 31

Alfa AF: 0.0000284 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.64		Gain of MoRF binding (P = 0.1233);
MVP		0.27
MPC		1.2
ClinPred		0.88	D
GERP RS		5.9
Varity_R		0.48
gMVP		0.76

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: rs372779694; hg19: chr12-7087510;