Variant chr15-58538351-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_000236.3(LIPC):c.107C>A(p.Ala36Asp) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A36V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

LIPC
NM_000236.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.688

Variant links:

Genes affected

LIPC (HGNC:6619): (lipase C, hepatic type) Enables phospholipase A1 activity and triglyceride lipase activity. Involved in several processes, including lipid homeostasis; plasma lipoprotein particle remodeling; and triglyceride catabolic process. Located in extracellular space. Implicated in several diseases, including Alzheimer's disease; coronary artery disease; familial combined hyperlipidemia; peripheral vascular disease; and type 2 diabetes mellitus. Biomarker of hyperinsulinism; obesity; and type 1 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

LIPC 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=0.23172694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3 linkuse as main transcript	c.107C>A	p.Ala36Asp	missense_variant	2/9	ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10 linkuse as main transcript	c.107C>A	p.Ala36Asp	missense_variant	2/9	1	NM_000236.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 28, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬† is likely to be tolerated. This variant has not been reported in the literature in individuals affected with LIPC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 36 of the LIPC protein (p.Ala36Asp). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.66

T;T;.;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.1

L;.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.84

N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.39

T;T;T;D

Sift4G

Benign

0.70

T;T;T;T

Polyphen

0.19

B;.;B;P

Vest4

0.25

MutPred

0.69

Gain of loop (P = 0.024);Gain of loop (P = 0.024);Gain of loop (P = 0.024);Gain of loop (P = 0.024);

MVP

0.87

MPC

0.13

ClinPred

0.14

GERP RS

3.2

Varity_R

0.067

gMVP

0.46

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over