12-6978659-T-C

Position:

chr12-6978659-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005768.6(LPCAT3):c.817A>G(p.Met273Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LPCAT3
NM_005768.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

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:

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 links:

LPCAT3 (HGNC:):

LPCAT3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14900294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPCAT3	NM_005768.6 linkuse as main transcript	c.817A>G	p.Met273Val	missense_variant	8/13	ENST00000261407.9	NP_005759.4	Q6P1A2-1
EMG1	NM_006331.8 linkuse as main transcript	c.*2850T>C		3_prime_UTR_variant	6/6	ENST00000599672.6	NP_006322.4	Q92979
EMG1	NM_001320049.2 linkuse as main transcript	c.*2850T>C		3_prime_UTR_variant	5/5		NP_001306978.1	Q92979
EMG1	NR_135131.2 linkuse as main transcript	n.632+3281T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LPCAT3	ENST00000261407.9 linkuse as main transcript	c.817A>G	p.Met273Val	missense_variant	8/13	1	NM_005768.6	ENSP00000261407.4	Q6P1A2-1
EMG1	ENST00000599672.6 linkuse as main transcript	c.*2850T>C		3_prime_UTR_variant	6/6	1	NM_006331.8	ENSP00000470560.1	Q92979
ENSG00000290146	ENST00000607161.5 linkuse as main transcript	n.624+3281T>C		intron_variant		2		ENSP00000480420.1	A0A087WWQ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251418

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2022

The c.817A>G (p.M273V) alteration is located in exon 8 (coding exon 8) of the LPCAT3 gene. This alteration results from a A to G substitution at nucleotide position 817, causing the methionine (M) at amino acid position 273 to be replaced by a valine (V). 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

0.088

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.020

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.72

M_CAP

Benign

0.0090

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.030

REVEL

Benign

0.087

Sift

Benign

0.37

Sift4G

Benign

0.80

Polyphen

0.0030

Vest4

0.33

MutPred

0.51

Loss of ubiquitination at K278 (P = 0.1223);

MVP

0.13

MPC

0.71

ClinPred

0.25

GERP RS

3.1

Varity_R

0.073

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over