chr15-58538351-C-A

Variant names:

• chr15-58538351-C-A
• rs1184798854
• NM_000236.3:c.107C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.688
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hyperlipidemia due to hepatic triglyceride lipase deficiency

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23172694).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. 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
	LIPC	NM_000236.3	MANE Select	c.107C>A	p.Ala36Asp	missense	Exon 2 of 9	NP_000227.2	P11150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.107C>A	p.Ala36Asp	missense	Exon 2 of 9	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.107C>A	p.Ala36Asp	missense	Exon 3 of 10	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.131-3434C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.69
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.18
Sift	Benign	0.39	T
Sift4G	Benign	0.70	T
Polyphen		0.19	B
Vest4		0.25
MutPred		0.69		Gain of loop (P = 0.024)
MVP		0.87
MPC		0.13
ClinPred		0.14	T
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

Other links and lift over

dbSNP: rs1184798854; hg19: chr15-58830550;