10-88669866-C-A

Variant names:

• chr10-88669866-C-A
• rs757492514
• NM_004190.4:c.452C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004190.4(LIPF):​c.452C>A​(p.Pro151Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P151L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: LIPF NM_004190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

LIPF (HGNC:6622): (lipase F, gastric type) This gene encodes gastric lipase, an enzyme involved in the digestion of dietary triglycerides in the gastrointestinal tract, and responsible for 30% of fat digestion processes occurring in human. It is secreted by gastric chief cells in the fundic mucosa of the stomach, and it hydrolyzes the ester bonds of triglycerides under acidic pH conditions. The gene is a member of a conserved gene family of lipases that play distinct roles in neutral lipid metabolism. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004190.4. 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
	LIPF	NM_004190.4	MANE Select	c.452C>A	p.Pro151Gln	missense	Exon 5 of 10	NP_004181.1	P07098-1
	LIPF	NM_001198829.2		c.482C>A	p.Pro161Gln	missense	Exon 6 of 11	NP_001185758.1	P07098-3
	LIPF	NM_001198830.2		c.383C>A	p.Pro128Gln	missense	Exon 6 of 11	NP_001185759.1	P07098-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPF	ENST00000238983.9	TSL:1 MANE Select	c.452C>A	p.Pro151Gln	missense	Exon 5 of 10	ENSP00000238983.5	P07098-1
	LIPF	ENST00000355843.2	TSL:1	c.383C>A	p.Pro128Gln	missense	Exon 6 of 11	ENSP00000348101.3	P07098-4
	LIPF	ENST00000394375.7	TSL:2	c.482C>A	p.Pro161Gln	missense	Exon 6 of 11	ENSP00000377900.3	P07098-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460708 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 726680

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111202

Other (OTH) AF: 0.0000166 AC: 1 AN: 60352

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.83
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	4.5	H
PhyloP100		3.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.74		Gain of catalytic residue at P151 (P = 0.0601)
MVP		0.88
MPC		0.57
ClinPred		1.0	D
GERP RS		3.2
Varity_R		0.92
gMVP		0.94
Mutation Taster		=54/46	polymorphism

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: rs757492514; hg19: chr10-90429623;