rs1049125

Positions:

• chr10-116609094-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000358834.9(PNLIPRP1):​c.1382T>C​(p.Leu461Pro) variant causes a missense change. The variant allele was found at a frequency of 0.18 in 1,611,582 control chromosomes in the GnomAD database, including 27,572 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2068 hom., cov: 33)
  • Exomes 𝑓: 0.18 (25504 hom.)
• Consequence: PNLIPRP1 ENST00000358834.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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]

LOC124902510 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017951727).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.1382T>C	p.Leu461Pro	missense_variant	13/13	ENST00000358834.9	NP_006220.1
LOC124902510	XR_007062299.1	n.483+171A>G		intron_variant, non_coding_transcript_variant
PNLIPRP1	NM_001303135.1	c.1382T>C	p.Leu461Pro	missense_variant	13/13		NP_001290064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.1382T>C	p.Leu461Pro	missense_variant	13/13	1	NM_006229.4	ENSP00000351695	P4

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22526 AN: 152140 Hom.: 2062 Cov.: 33

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.178 AC: 44646 AN: 250284 Hom.: 4366 AF XY: 0.176 AC XY: 23848 AN XY: 135346

Gnomad AFR exome AF: 0.0358

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.130

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.183 AC: 267030 AN: 1459324 Hom.: 25504 Cov.: 30 AF XY: 0.181 AC XY: 131716 AN XY: 726108

Gnomad4 AFR exome AF: 0.0321

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.148 AC: 22540 AN: 152258 Hom.: 2068 Cov.: 33 AF XY: 0.151 AC XY: 11213 AN XY: 74444

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.158

Alfa AF: 0.180 Hom.: 3440

Bravo AF: 0.147

TwinsUK AF: 0.196 AC: 726

ALSPAC AF: 0.193 AC: 745

ESP6500AA AF: 0.0461 AC: 203

ESP6500EA AF: 0.190 AC: 1634

ExAC AF: 0.174 AC: 21188

Asia WGS AF: 0.144 AC: 503 AN: 3478

EpiCase AF: 0.191

EpiControl AF: 0.196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.86	.;D;D
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M;M;.
MutationTaster	Benign	0.00013	P;P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.4	D;D;D
REVEL	Benign	0.23
Sift	Benign	0.087	T;T;T
Sift4G	Benign	0.061	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.35
MPC		0.13
ClinPred		0.074	T
GERP RS		4.0
Varity_R		0.89
gMVP		0.67

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: rs1049125; hg19: chr10-118368606; COSMIC: COSV62611325;