Genetic Variant NM_153613.3:c.1400G>C (chr15-34359302-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_153613.3(LPCAT4):c.1400G>C(p.Cys467Ser) variant causes a missense, splice region 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. 15/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

LPCAT4
NM_153613.3 missense, splice_region

Scores

Splicing: ADA: 0.07788

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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=0.11393684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPCAT4	NM_153613.3 link	c.1400G>C	p.Cys467Ser	missense_variant, splice_region_variant	Exon 14 of 14	ENST00000314891.11	NP_705841.2	Q643R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LPCAT4	ENST00000314891.11 link	c.1400G>C	p.Cys467Ser	missense_variant, splice_region_variant	Exon 14 of 14	1	NM_153613.3	ENSP00000317300.6	Q643R3
LPCAT4	ENST00000563748.5 link	n.964G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	2
LPCAT4	ENST00000567507.1 link	n.*211G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000454422.1	H3BMK4
LPCAT4	ENST00000567507.1 link	n.*211G>C		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000454422.1	H3BMK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000900

AC:

AN:

111170

Hom.:

AF XY:

0.0000176

AC XY:

AN XY:

56866

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:

0.0000222

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000995

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1400G>C (p.C467S) alteration is located in exon 14 (coding exon 14) of the LPCAT4 gene. This alteration results from a G to C substitution at nucleotide position 1400, causing the cysteine (C) at amino acid position 467 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

0.076

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.65

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.76

N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.87

N;.

REVEL

Benign

0.21

Sift

Benign

0.72

T;.

Sift4G

Benign

0.37

T;T

Polyphen

0.0050

B;.

Vest4

0.17

MutPred

0.50

Gain of disorder (P = 0.0014);.;

MVP

0.27

MPC

0.010

ClinPred

0.10

GERP RS

2.2

Varity_R

0.040

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.078

dbscSNV1_RF

Benign

0.37

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -5

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