10-88675596-A-T

Position:

• chr10-88675596-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004190.4(LIPF):​c.827A>T​(p.Asp276Val) variant causes a missense change. 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)
  • Exomes 𝑓: 0.000087 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIPF NM_004190.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPF	NM_004190.4	c.827A>T	p.Asp276Val	missense_variant	8/10	ENST00000238983.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPF	ENST00000238983.9	c.827A>T	p.Asp276Val	missense_variant	8/10	1	NM_004190.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000874 AC: 117 AN: 1338666 Hom.: 0 Cov.: 27 AF XY: 0.0000836 AC XY: 56 AN XY: 670234

Gnomad4 AFR exome AF: 0.0000647

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.000208

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.0000205

Gnomad4 NFE exome AF: 0.000101

Gnomad4 OTH exome AF: 0.0000729

GnomAD4 genome Cov.: 32

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

Dec 03, 2021

The c.857A>T (p.D286V) alteration is located in exon 9 (coding exon 8) of the LIPF gene. This alteration results from a A to T substitution at nucleotide position 857, causing the aspartic acid (D) at amino acid position 286 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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	0.045	D
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-7.2	D;.;D;.
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;.;D;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.62
MutPred		0.64		.;.;Gain of sheet (P = 0.0827);.;
MVP		0.90
MPC		0.70
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.94
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: -10

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: chr10-90435353;