10-88668729-C-A

Variant names:

• chr10-88668729-C-A
• rs563382413
• NM_004190.4:c.395C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_004190.4(LIPF):​c.395C>A​(p.Pro132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: LIPF NM_004190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.610
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30425468).

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.395C>A	p.Pro132Gln	missense	Exon 4 of 10	NP_004181.1	P07098-1
	LIPF	NM_001198829.2		c.425C>A	p.Pro142Gln	missense	Exon 5 of 11	NP_001185758.1	P07098-3
	LIPF	NM_001198830.2		c.326C>A	p.Pro109Gln	missense	Exon 5 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.395C>A	p.Pro132Gln	missense	Exon 4 of 10	ENSP00000238983.5	P07098-1
	LIPF	ENST00000355843.2	TSL:1	c.326C>A	p.Pro109Gln	missense	Exon 5 of 11	ENSP00000348101.3	P07098-4
	LIPF	ENST00000609378.1	TSL:1	n.456C>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250834 AF XY: 0.00000737

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461702 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727136

African (AFR) AF: 0.000358 AC: 12 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111886

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74474

African (AFR) AF: 0.0000481 AC: 2 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		0.61
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.45
Sift	Benign	0.040	D
Sift4G	Uncertain	0.056	T
Polyphen		1.0	D
Vest4		0.29
MutPred		0.50		Gain of MoRF binding (P = 0.0794)
MVP		0.85
MPC		0.35
ClinPred		0.76	D
GERP RS		3.8
Varity_R		0.35
gMVP		0.80
Mutation Taster		=74/26	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: rs563382413; hg19: chr10-90428486;