10-116596294-C-G

Position:

• chr10-116596294-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006229.4(PNLIPRP1):​c.546C>G​(p.Ser182Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.953

Genes affected

PNLIPRP1 (HGNC:9156): (pancreatic lipase related protein 1) Predicted to enable calcium ion binding activity. Predicted to be involved in lipid catabolic process. Predicted to be located in extracellular region. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079662144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNLIPRP1	NM_006229.4	c.546C>G	p.Ser182Arg	missense_variant	6/13	ENST00000358834.9
PNLIPRP1	NM_001303135.1	c.546C>G	p.Ser182Arg	missense_variant	6/13
PNLIPRP1	XM_047425364.1	c.546C>G	p.Ser182Arg	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.546C>G	p.Ser182Arg	missense_variant	6/13	1	NM_006229.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461002 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726888

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.546C>G (p.S182R) alteration is located in exon 6 (coding exon 5) of the PNLIPRP1 gene. This alteration results from a C to G substitution at nucleotide position 546, causing the serine (S) at amino acid position 182 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	1.0
DANN	Benign	0.082
DEOGEN2	Benign	0.25	T;T;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.65	T;.;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.080	T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	-0.46	.;N;N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	2.5	N;N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0010	.;B;B;.;.
Vest4		0.14, 0.14
MutPred		0.49		Loss of glycosylation at S182 (P = 0.0122);Loss of glycosylation at S182 (P = 0.0122);Loss of glycosylation at S182 (P = 0.0122);.;Loss of glycosylation at S182 (P = 0.0122);
MVP		0.63
MPC		0.044
ClinPred		0.034	T
GERP RS		-0.66
Varity_R		0.18
gMVP		0.60

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

Other links and lift over

dbSNP: rs1847734709; hg19: chr10-118355806;