Genetic Variant LPCAT1:p.Ser356Pro (chr5-1474070-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024830.5(LPCAT1):c.1066T>C(p.Ser356Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S356A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LPCAT1
NM_024830.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.782

Publications

0 publications found

Variant links:

Genes affected

LPCAT1 (HGNC:25718): (lysophosphatidylcholine acyltransferase 1) This gene encodes a member of the 1-acyl-sn-glycerol-3-phosphate acyltransferase family of proteins. The encoded enzyme plays a role in phospholipid metabolism, specifically in the conversion of lysophosphatidylcholine to phosphatidylcholine in the presence of acyl-CoA. This process is important in the synthesis of lung surfactant and platelet-activating factor (PAF). Elevated expression of this gene may contribute to the progression of oral squamous cell, prostate, breast, and other human cancers. [provided by RefSeq, Sep 2016]

LPCAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26914817).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024830.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT1	NM_024830.5	MANE Select	c.1066T>C	p.Ser356Pro	missense	Exon 11 of 14	NP_079106.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LPCAT1	ENST00000283415.4	TSL:1 MANE Select	c.1066T>C	p.Ser356Pro	missense	Exon 11 of 14	ENSP00000283415.3	Q8NF37
LPCAT1	ENST00000934191.1		c.1162T>C	p.Ser388Pro	missense	Exon 12 of 15	ENSP00000604250.1
LPCAT1	ENST00000934189.1		c.1153T>C	p.Ser385Pro	missense	Exon 12 of 15	ENSP00000604248.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.63

M_CAP

Benign

0.030

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.2

PhyloP100

0.78

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.3

REVEL

Benign

0.16

Sift

Uncertain

0.011

Sift4G

Benign

0.17

Polyphen

0.0080

Vest4

0.41

MutPred

0.56

Loss of phosphorylation at S356 (P = 0.0035)

MVP

0.52

MPC

0.79

ClinPred

0.39

GERP RS

0.44

Varity_R

0.25

gMVP

0.78

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over