chr10-88668642-C-A

Variant names:

• chr10-88668642-C-A
• NM_004190.4:c.308C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004190.4(LIPF):​c.308C>A​(p.Ala103Asp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPF NM_004190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.671
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

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.308C>A	p.Ala103Asp	missense	Exon 4 of 10	NP_004181.1	P07098-1
	LIPF	NM_001198829.2		c.338C>A	p.Ala113Asp	missense	Exon 5 of 11	NP_001185758.1	P07098-3
	LIPF	NM_001198830.2		c.254-15C>A		intron	N/A	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.308C>A	p.Ala103Asp	missense	Exon 4 of 10	ENSP00000238983.5	P07098-1
	LIPF	ENST00000355843.2	TSL:1	c.254-15C>A		intron	N/A	ENSP00000348101.3	P07098-4
	LIPF	ENST00000609378.1	TSL:1	n.369C>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		0.67
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.96	D
Vest4		0.74
MutPred		0.83		Gain of sheet (P = 0.0827)
MVP		0.91
MPC		0.69
ClinPred		0.99	D
GERP RS		-1.5
Varity_R		0.98
gMVP		0.98
Mutation Taster		=57/43	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

hg19: chr10-90428399;