10-116592536-T-C

Variant names:

• chr10-116592536-T-C
• NM_006229.4:c.325T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006229.4(PNLIPRP1):​c.325T>C​(p.Cys109Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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 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, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.325T>C	p.Cys109Arg	missense_variant	Exon 4 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.325T>C	p.Cys109Arg	missense_variant	Exon 4 of 13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.325T>C	p.Cys109Arg	missense_variant	Exon 4 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.325T>C	p.Cys109Arg	missense_variant	Exon 4 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.325T>C (p.C109R) alteration is located in exon 4 (coding exon 3) of the PNLIPRP1 gene. This alteration results from a T to C substitution at nucleotide position 325, causing the cysteine (C) at amino acid position 109 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	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D;D;D;.;D;D;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T;.;T;T;T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	0.93	.;L;L;.;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-12	D;D;D;D;D;D;D
REVEL	Pathogenic	0.81
Sift	Benign	0.086	T;D;D;D;D;D;D
Sift4G	Benign	0.26	T;T;T;D;D;D;T
Polyphen		1.0	.;D;D;.;.;.;.
Vest4		0.91, 0.92
MutPred		0.74		Loss of methylation at K110 (P = 0.0153);Loss of methylation at K110 (P = 0.0153);Loss of methylation at K110 (P = 0.0153);Loss of methylation at K110 (P = 0.0153);Loss of methylation at K110 (P = 0.0153);Loss of methylation at K110 (P = 0.0153);Loss of methylation at K110 (P = 0.0153);
MVP		0.99
MPC		0.36
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.98
gMVP		0.68

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: chr10-118352048;