10-116549731-A-G

Variant names:

• chr10-116549731-A-G
• rs3010503
• NM_000936.4:c.324+1249A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• pancreatic triacylglycerol lipase deficiency

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PNLIP	NM_000936.4	c.324+1249A>G		intron_variant	Intron 4 of 12	ENST00000369221.2	NP_000927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIP	ENST00000369221.2	c.324+1249A>G		intron_variant	Intron 4 of 12	1	NM_000936.4	ENSP00000358223.2
PNLIP	ENST00000470562.1	n.324+1249A>G		intron_variant	Intron 3 of 3	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

African (AFR) AF: 0.868 AC: 36030 AN: 41526

American (AMR) AF: 0.864 AC: 13204 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3058 AN: 3468

East Asian (EAS) AF: 0.615 AC: 3163 AN: 5140

South Asian (SAS) AF: 0.919 AC: 4424 AN: 4814

European-Finnish (FIN) AF: 0.914 AC: 9673 AN: 10586

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62503 AN: 68014

Other (OTH) AF: 0.901 AC: 1902 AN: 2112

Alfa AF: 0.899 Hom.: 95696

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
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs3010503; hg19: chr10-118309243;