NM_001011709.3:c.583C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001011709.3(PNLIPRP3):​c.583C>G​(p.Pro195Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P195T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PNLIPRP3
NM_001011709.3 missense

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.83
Variant links:
Genes affected
PNLIPRP3 (HGNC:23492): (pancreatic lipase related protein 3) Predicted to enable triglyceride lipase activity. Predicted to be involved in lipid catabolic process. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PNLIPRP3NM_001011709.3 linkc.583C>G p.Pro195Ala missense_variant Exon 6 of 12 ENST00000369230.4 NP_001011709.2 Q17RR3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PNLIPRP3ENST00000369230.4 linkc.583C>G p.Pro195Ala missense_variant Exon 6 of 12 1 NM_001011709.3 ENSP00000358232.3 Q17RR3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460422
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726544
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.61
D
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.042
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Uncertain
0.55
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Benign
0.42
T
PROVEAN
Pathogenic
-6.7
D
REVEL
Uncertain
0.53
Sift
Benign
0.18
T
Sift4G
Benign
0.076
T
Polyphen
1.0
D
Vest4
0.54
MutPred
0.88
Loss of glycosylation at P195 (P = 0.0965);
MVP
0.87
MPC
0.29
ClinPred
0.99
D
GERP RS
4.0
Varity_R
0.21
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-118220495; API