10-88673699-A-G

Variant names:

• chr10-88673699-A-G
• NM_004190.4:c.781A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004190.4(LIPF):​c.781A>G​(p.Ile261Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LIPF NM_004190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.30

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063574225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPF	NM_004190.4	c.781A>G	p.Ile261Val	missense_variant	Exon 7 of 10	ENST00000238983.9	NP_004181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPF	ENST00000238983.9	c.781A>G	p.Ile261Val	missense_variant	Exon 7 of 10	1	NM_004190.4	ENSP00000238983.5
LIPF	ENST00000355843.2	c.712A>G	p.Ile238Val	missense_variant	Exon 8 of 11	1		ENSP00000348101.3
LIPF	ENST00000394375.7	c.811A>G	p.Ile271Val	missense_variant	Exon 8 of 11	2		ENSP00000377900.3
LIPF	ENST00000608620.5	c.682A>G	p.Ile228Val	missense_variant	Exon 7 of 10	2		ENSP00000477140.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461136 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726894

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.811A>G (p.I271V) alteration is located in exon 8 (coding exon 7) of the LIPF gene. This alteration results from a A to G substitution at nucleotide position 811, causing the isoleucine (I) at amino acid position 271 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.3
DANN	Benign	0.88
DEOGEN2	Benign	0.0028	.;.;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.21	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.064	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;.;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.47	N;.;N;.
REVEL	Benign	0.047
Sift	Benign	0.21	T;.;T;.
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0020	.;.;B;.
Vest4		0.095
MutPred		0.51		.;.;Gain of sheet (P = 0.1945);.;
MVP		0.36
MPC		0.11
ClinPred		0.032	T
GERP RS		-2.9
Varity_R		0.11
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-90433456;