12-6977497-G-A

Position:

chr12-6977497-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005768.6(LPCAT3):c.1217C>T(p.Thr406Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.000024 ( 0 hom. )

Consequence

LPCAT3
NM_005768.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0430

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:

ENSG00000290146 (HGNC:):

ENSG00000290146 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066848636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPCAT3	NM_005768.6 linkuse as main transcript	c.1217C>T	p.Thr406Ile	missense_variant	11/13	ENST00000261407.9	NP_005759.4	Q6P1A2-1
EMG1	NM_006331.8 linkuse as main transcript	c.*1688G>A		3_prime_UTR_variant	6/6	ENST00000599672.6	NP_006322.4	Q92979
EMG1	NM_001320049.2 linkuse as main transcript	c.*1688G>A		3_prime_UTR_variant	5/5		NP_001306978.1	Q92979
EMG1	NR_135131.2 linkuse as main transcript	n.632+2119G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LPCAT3	ENST00000261407.9 linkuse as main transcript	c.1217C>T	p.Thr406Ile	missense_variant	11/13	1	NM_005768.6	ENSP00000261407.4	Q6P1A2-1
EMG1	ENST00000599672.6 linkuse as main transcript	c.*1688G>A		3_prime_UTR_variant	6/6	1	NM_006331.8	ENSP00000470560.1	Q92979
ENSG00000290146	ENST00000607161.5 linkuse as main transcript	n.624+2119G>A		intron_variant		2		ENSP00000480420.1	A0A087WWQ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251382

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727246

show subpopulations

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:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Oct 27, 2022

The c.1217C>T (p.T406I) alteration is located in exon 11 (coding exon 11) of the LPCAT3 gene. This alteration results from a C to T substitution at nucleotide position 1217, causing the threonine (T) at amino acid position 406 to be replaced by an isoleucine (I). 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

0.065

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.010

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.64

M_CAP

Benign

0.019

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.040

REVEL

Benign

0.027

Sift

Benign

0.34

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.065

MVP

0.043

MPC

0.76

ClinPred

0.016

GERP RS

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.091

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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