NM_000936.4:c.1334+1121A>G

Variant names:

• chr10-116562757-A-G
• rs2915772
• NM_000936.4:c.1334+1121A>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.1334+1121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,210 control chromosomes in the GnomAD database, including 59,993 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 (59993 hom., cov: 32)
• Consequence: PNLIP NM_000936.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 2 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=-1.0).
• 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.1334+1121A>G		intron_variant	Intron 12 of 12	ENST00000369221.2	NP_000927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIP	ENST00000369221.2	c.1334+1121A>G		intron_variant	Intron 12 of 12	1	NM_000936.4	ENSP00000358223.2

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134746 AN: 152092 Hom.: 59950 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.886 AC: 134843 AN: 152210 Hom.: 59993 Cov.: 32 AF XY: 0.884 AC XY: 65771 AN XY: 74396

African (AFR) AF: 0.857 AC: 35592 AN: 41516

American (AMR) AF: 0.863 AC: 13193 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3062 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3308 AN: 5166

South Asian (SAS) AF: 0.919 AC: 4428 AN: 4818

European-Finnish (FIN) AF: 0.913 AC: 9683 AN: 10600

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62495 AN: 68022

Other (OTH) AF: 0.900 AC: 1903 AN: 2114

Alfa AF: 0.908 Hom.: 77787

Bravo AF: 0.878

Asia WGS AF: 0.815 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.53
PhyloP100		-0.93
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: rs2915772; hg19: chr10-118322269;