Genetic Variant NM_005768.6:c.536G>C (chr12-6981145-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005768.6(LPCAT3):c.536G>C(p.Arg179Pro) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LPCAT3
NM_005768.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.602

Publications

0 publications found

Variant links:

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]

LPCAT3 links:

ENSG00000290146 (HGNC:):

ENSG00000290146 links:

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]

EMG1 Gene-Disease associations (from GenCC):

Bowen-Conradi syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

EMG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.08477363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005768.6. 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
	LPCAT3	NM_005768.6	MANE Select	c.536G>C	p.Arg179Pro	missense	Exon 6 of 13	NP_005759.4
	EMG1	NR_135131.2		n.632+5767C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LPCAT3	ENST00000261407.9	TSL:1 MANE Select	c.536G>C	p.Arg179Pro	missense	Exon 6 of 13	ENSP00000261407.4	Q6P1A2-1
LPCAT3	ENST00000535479.5	TSL:1	n.536G>C		non_coding_transcript_exon	Exon 6 of 11	ENSP00000438765.1	F5H0M4
LPCAT3	ENST00000540090.5	TSL:1	n.*63G>C		non_coding_transcript_exon	Exon 4 of 8	ENSP00000442454.1	F5H7K7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.023

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.67

M_CAP

Benign

0.013

MetaRNN

Benign

0.085

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.66

PhyloP100

0.60

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

REVEL

Benign

0.14

Sift

Benign

0.36

Sift4G

Benign

0.35

Polyphen

0.0020

Vest4

0.20

MutPred

0.46

Gain of methylation at K175 (P = 0.0321)

MVP

0.11

MPC

1.0

ClinPred

0.24

GERP RS

3.9

Varity_R

0.42

gMVP

0.71

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over