rs1049125

Variant names:

• chr10-116609094-T-C
• rs1049125
• NM_006229.4:c.1382T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006229.4(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.

• Frequency:
  • Genomes: 𝑓 0.15 (2068 hom., cov: 33)
  • Exomes 𝑓: 0.18 (25504 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 17 publications found

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]

ENSG00000309420 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006229.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP1	NM_006229.4	MANE Select	c.1382T>C	p.Leu461Pro	missense	Exon 13 of 13	NP_006220.1
	PNLIPRP1	NM_001303135.1		c.1382T>C	p.Leu461Pro	missense	Exon 13 of 13	NP_001290064.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP1	ENST00000358834.9	TSL:1 MANE Select	c.1382T>C	p.Leu461Pro	missense	Exon 13 of 13	ENSP00000351695.4
	PNLIPRP1	ENST00000525820.5	TSL:1	n.3178T>C		non_coding_transcript_exon	Exon 12 of 12
	PNLIPRP1	ENST00000526223.5	TSL:1	n.3334T>C		non_coding_transcript_exon	Exon 12 of 12

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

GnomAD2 exomes AF: 0.178 AC: 44646 AN: 250284 AF XY: 0.176

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 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

African (AFR) AF: 0.0321 AC: 1073 AN: 33446

American (AMR) AF: 0.253 AC: 11292 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4626 AN: 26054

East Asian (EAS) AF: 0.134 AC: 5306 AN: 39664

South Asian (SAS) AF: 0.123 AC: 10586 AN: 86138

European-Finnish (FIN) AF: 0.196 AC: 10427 AN: 53236

Middle Eastern (MID) AF: 0.162 AC: 936 AN: 5762

European-Non Finnish (NFE) AF: 0.191 AC: 212203 AN: 1110134

Other (OTH) AF: 0.175 AC: 10581 AN: 60302

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

African (AFR) AF: 0.0368 AC: 1529 AN: 41580

American (AMR) AF: 0.207 AC: 3172 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3466

East Asian (EAS) AF: 0.147 AC: 761 AN: 5186

South Asian (SAS) AF: 0.124 AC: 600 AN: 4820

European-Finnish (FIN) AF: 0.198 AC: 2096 AN: 10602

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13210 AN: 67984

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.170 Hom.: 5865

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 v4.9

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
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.23
Sift	Benign	0.087	T
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.35
MPC		0.13
ClinPred		0.074	T
GERP RS		4.0
Varity_R		0.89
gMVP		0.67
Mutation Taster		=99/1	polymorphism (auto)

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