rs3010503

Positions:

• chr10-116549731-A-G
• chr10-116549731-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000936.4(PNLIP):​c.324+1249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,154 control chromosomes in the GnomAD database, including 60,310 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60310 hom., cov: 32)
• Consequence: PNLIP NM_000936.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924

Genes affected

PNLIP (HGNC:9155): (pancreatic lipase) This gene encodes a member of the lipase family of proteins. The encoded enzyme is secreted by the pancreas and hydrolyzes triglycerides in the small intestine, and is essential for the efficient digestion of dietary fats. Inhibition of the encoded enzyme may prevent high-fat diet-induced obesity in mice and result in weight loss in human patients with obesity. Mutations in this gene cause congenital pancreatic lipase deficiency, a rare disorder characterized by steatorrhea. [provided by RefSeq, Jul 2016]

PNLIP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNLIP	NM_000936.4	c.324+1249A>G		intron_variant		ENST00000369221.2	NP_000927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNLIP	ENST00000369221.2	c.324+1249A>G		intron_variant		1	NM_000936.4	ENSP00000358223.2
PNLIP	ENST00000470562.1	n.324+1249A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135034 AN: 152034 Hom.: 60264 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.906

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.888 AC: 135135 AN: 152154 Hom.: 60310 Cov.: 32 AF XY: 0.886 AC XY: 65909 AN XY: 74376

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.901

Alfa AF: 0.906 Hom.: 14195

Bravo AF: 0.880

Asia WGS AF: 0.800 AC: 2782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.52
DANN	Benign	0.47

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: rs3010503; hg19: chr10-118309243;