Genetic Variant NM_153613.3:c.1304C>A (chr15-34359684-G-T) – 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.1304C>A(p.Thr435Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,460 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.000013 ( 1 hom. )

Consequence

LPCAT4
NM_153613.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

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:

Genome browser will be placed here

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=0.2450544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPCAT4	NM_153613.3 link	c.1304C>A	p.Thr435Asn	missense_variant	Exon 13 of 14	ENST00000314891.11	NP_705841.2	Q643R3
LPCAT4	XM_047432334.1 link	c.*63C>A		3_prime_UTR_variant	Exon 14 of 14		XP_047288290.1
LPCAT4	XR_007064436.1 link	n.1267C>A		non_coding_transcript_exon_variant	Exon 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LPCAT4	ENST00000314891.11 link	c.1304C>A	p.Thr435Asn	missense_variant	Exon 13 of 14	1	NM_153613.3	ENSP00000317300.6	Q643R3
LPCAT4	ENST00000563748.5 link	n.868C>A		non_coding_transcript_exon_variant	Exon 4 of 5	2
LPCAT4	ENST00000567507.1 link	n.*115C>A		non_coding_transcript_exon_variant	Exon 4 of 5	3		ENSP00000454422.1	H3BMK4
LPCAT4	ENST00000567507.1 link	n.*115C>A		3_prime_UTR_variant	Exon 4 of 5	3		ENSP00000454422.1	H3BMK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250774

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135580

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:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461460

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727008

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:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1304C>A (p.T435N) alteration is located in exon 13 (coding exon 13) of the LPCAT4 gene. This alteration results from a C to A substitution at nucleotide position 1304, causing the threonine (T) at amino acid position 435 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

0.094

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.23

Sift

Benign

0.032

D;.

Sift4G

Benign

0.40

T;T

Polyphen

0.031

B;.

Vest4

0.51

MutPred

0.30

Loss of ubiquitination at K430 (P = 0.1498);.;

MVP

0.14

MPC

0.011

ClinPred

0.11

GERP RS

5.6

Varity_R

0.20

gMVP

0.38

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