NM_001011709.3:c.583C>T

Variant names:

• chr10-116460983-C-T
• rs544377195
• NM_001011709.3:c.583C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001011709.3(PNLIPRP3):​c.583C>T​(p.Pro195Ser) 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 𝑓: 6.8e-7 (0 hom.)
• Consequence: PNLIPRP3 NM_001011709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP3	NM_001011709.3	MANE Select	c.583C>T	p.Pro195Ser	missense	Exon 6 of 12	NP_001011709.2	Q17RR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP3	ENST00000369230.4	TSL:1 MANE Select	c.583C>T	p.Pro195Ser	missense	Exon 6 of 12	ENSP00000358232.3	Q17RR3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460422 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726544

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 38376

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.085	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Pathogenic	3.5	H
PhyloP100		2.8
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.91		Gain of sheet (P = 0.1208)
MVP		0.88
MPC		0.29
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.69
gMVP		0.78
Mutation Taster		=81/19	polymorphism

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: rs544377195; hg19: chr10-118220495;