Variant 15-34361504-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153613.3(LPCAT4):c.1039G>T(p.Ala347Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,652 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: 0.0000055 ( 0 hom. )

Consequence

LPCAT4
NM_153613.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

LPCAT4 (HGNC:30059): (lysophosphatidylcholine acyltransferase 4) Members of the 1-acylglycerol-3-phosphate O-acyltransferase (EC 2.3.1.51) family, such as AGPAT7, catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), a precursor in the biosynthesis of all glycerolipids. Both LPA and PA are involved in signal transduction (Ye et al., 2005 [PubMed 16243729]).[supplied by OMIM, May 2008]

LPCAT4 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=0.22995621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LPCAT4	NM_153613.3 linkuse as main transcript	c.1039G>T	p.Ala347Ser	missense_variant	11/14	ENST00000314891.11	NP_705841.2
LPCAT4	XM_047432334.1 linkuse as main transcript	c.1039G>T	p.Ala347Ser	missense_variant	11/14		XP_047288290.1
LPCAT4	XM_006720454.2 linkuse as main transcript	c.1039G>T	p.Ala347Ser	missense_variant	11/14		XP_006720517.1
LPCAT4	XR_007064436.1 linkuse as main transcript	n.1106+692G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LPCAT4	ENST00000314891.11 linkuse as main transcript	c.1039G>T	p.Ala347Ser	missense_variant	11/14	1	NM_153613.3	ENSP00000317300	P1
LPCAT4	ENST00000563240.1 linkuse as main transcript	n.347G>T		non_coding_transcript_exon_variant	4/4	2
LPCAT4	ENST00000563748.5 linkuse as main transcript	n.238G>T		non_coding_transcript_exon_variant	3/5	2
LPCAT4	ENST00000567507.1 linkuse as main transcript	c.209+692G>T		intron_variant, NMD_transcript_variant		3		ENSP00000454422

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000314

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

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

Dec 27, 2023

The c.1039G>T (p.A347S) alteration is located in exon 11 (coding exon 11) of the LPCAT4 gene. This alteration results from a G to T substitution at nucleotide position 1039, causing the alanine (A) at amino acid position 347 to be replaced by a serine (S). 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

0.090

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-0.093

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

0.56

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.79

N;.

REVEL

Benign

0.20

Sift

Benign

0.18

T;.

Sift4G

Benign

0.45

T;T

Polyphen

0.10

B;.

Vest4

0.48

MutPred

0.34

Gain of loop (P = 0.0045);.;

MVP

0.42

MPC

0.65

ClinPred

0.56

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.45

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

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