chr10-88669913-C-T

Position:

• chr10-88669913-C-T

Variant summary

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

The NM_004190.4(LIPF):​c.499C>T​(p.His167Tyr) 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. 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: 0.921

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 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=0.086940676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPF	NM_004190.4	c.499C>T	p.His167Tyr	missense_variant	5/10	ENST00000238983.9	NP_004181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPF	ENST00000238983.9	c.499C>T	p.His167Tyr	missense_variant	5/10	1	NM_004190.4	ENSP00000238983	P1
LIPF	ENST00000355843.2	c.430C>T	p.His144Tyr	missense_variant	6/11	1		ENSP00000348101
LIPF	ENST00000394375.7	c.529C>T	p.His177Tyr	missense_variant	6/11	2		ENSP00000377900
LIPF	ENST00000608620.5	c.400C>T	p.His134Tyr	missense_variant	5/10	2		ENSP00000477140

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.529C>T (p.H177Y) alteration is located in exon 6 (coding exon 5) of the LIPF gene. This alteration results from a C to T substitution at nucleotide position 529, causing the histidine (H) at amino acid position 177 to be replaced by a tyrosine (Y). 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	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.1
DANN	Benign	0.17
DEOGEN2	Benign	0.0022	.;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.68	T;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;.;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	2.5	N;.;N;.
REVEL	Benign	0.097
Sift	Benign	1.0	T;.;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0030	.;.;B;.
Vest4		0.18
MutPred		0.64		.;.;Loss of disorder (P = 0.0349);.;
MVP		0.25
MPC		0.15
ClinPred		0.054	T
GERP RS		-1.7
Varity_R		0.14
gMVP		0.88

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: rs1841569196; hg19: chr10-90429670;