Menu
GeneBe

10-116547343-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000936.4(PNLIP):c.96A>C(p.Pro32=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,614,094 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 28 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 32 hom. )

Consequence

PNLIP
NM_000936.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.76
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-116547343-A-C is Benign according to our data. Variant chr10-116547343-A-C is described in ClinVar as [Benign]. Clinvar id is 768391.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.76 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1781/152274) while in subpopulation AFR AF= 0.0401 (1668/41548). AF 95% confidence interval is 0.0385. There are 28 homozygotes in gnomad4. There are 877 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PNLIPNM_000936.4 linkuse as main transcriptc.96A>C p.Pro32= synonymous_variant 3/13 ENST00000369221.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PNLIPENST00000369221.2 linkuse as main transcriptc.96A>C p.Pro32= synonymous_variant 3/131 NM_000936.4 P1
PNLIPENST00000470562.1 linkuse as main transcriptn.96A>C non_coding_transcript_exon_variant 2/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0117
AC:
1778
AN:
152156
Hom.:
28
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0402
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00504
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.0129
GnomAD3 exomes
AF:
0.00305
AC:
768
AN:
251470
Hom.:
14
AF XY:
0.00230
AC XY:
313
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.0417
Gnomad AMR exome
AF:
0.00188
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000105
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00131
AC:
1917
AN:
1461820
Hom.:
32
Cov.:
30
AF XY:
0.00111
AC XY:
810
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.0467
Gnomad4 AMR exome
AF:
0.00192
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000504
Gnomad4 OTH exome
AF:
0.00316
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0117
AC:
1781
AN:
152274
Hom.:
28
Cov.:
32
AF XY:
0.0118
AC XY:
877
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0401
Gnomad4 AMR
AF:
0.00503
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.00488
Hom.:
8
Bravo
AF:
0.0133
Asia WGS
AF:
0.00433
AC:
15
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
0.060
Dann
Benign
0.51

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76246039; hg19: chr10-118306855; API