NM_000236.3:c.137A>C

Variant names:

• chr15-58538381-A-C
• rs1276070198
• NM_000236.3:c.137A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000236.3(LIPC):​c.137A>C​(p.His46Pro) 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. 16/21 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. H46Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPC NM_000236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721

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]

ACMG classification

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=0.15550277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.137A>C	p.His46Pro	missense_variant	Exon 2 of 9	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.137A>C	p.His46Pro	missense_variant	Exon 2 of 9	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000209 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	6.1
DANN	Benign	0.93
DEOGEN2	Benign	0.35	T;.;T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.56	T;T;.;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.29	N;.;N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.86	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.36	T;T;T;T
Polyphen		0.0010	B;.;B;P
Vest4		0.19
MutPred		0.43		Gain of glycosylation at H46 (P = 0.0315);Gain of glycosylation at H46 (P = 0.0315);Gain of glycosylation at H46 (P = 0.0315);Gain of glycosylation at H46 (P = 0.0315);
MVP		0.91
MPC		0.11
ClinPred		0.34	T
GERP RS		2.6
Varity_R		0.076
gMVP		0.67

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

Other links and lift over

dbSNP: rs1276070198; hg19: chr15-58830580;