rs2305204

Variant names:

• chr10-116605455-G-C
• rs2305204
• NM_006229.4:c.1242G>C

Variant summary

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

The NM_006229.4(PNLIPRP1):​c.1242G>C​(p.Glu414Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,610,726 control chromosomes in the GnomAD database, including 7,459 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.065 (701 hom., cov: 33)
  • Exomes 𝑓: 0.076 (6758 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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=0.003960341).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.1242G>C	p.Glu414Asp	missense_variant	Exon 12 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.1242G>C	p.Glu414Asp	missense_variant	Exon 12 of 13		NP_001290064.1
LOC124902510	XR_007062299.1	n.1932C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.1242G>C	p.Glu414Asp	missense_variant	Exon 12 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes AF: 0.0648 AC: 9857 AN: 152054 Hom.: 705 Cov.: 33

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0789

GnomAD3 exomes AF: 0.0930 AC: 23354 AN: 251198 Hom.: 2398 AF XY: 0.0944 AC XY: 12816 AN XY: 135772

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.0442

Gnomad ASJ exome AF: 0.0733

Gnomad EAS exome AF: 0.442

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.0667

Gnomad NFE exome AF: 0.0668

Gnomad OTH exome AF: 0.0920

GnomAD4 exome AF: 0.0757 AC: 110477 AN: 1458554 Hom.: 6758 Cov.: 29 AF XY: 0.0765 AC XY: 55481 AN XY: 725610

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.0457

Gnomad4 ASJ exome AF: 0.0796

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0667

Gnomad4 NFE exome AF: 0.0645

Gnomad4 OTH exome AF: 0.0923

GnomAD4 genome AF: 0.0647 AC: 9851 AN: 152172 Hom.: 701 Cov.: 33 AF XY: 0.0674 AC XY: 5016 AN XY: 74380

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0506

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0662

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0748 Hom.: 517

Bravo AF: 0.0643

TwinsUK AF: 0.0653 AC: 242

ALSPAC AF: 0.0646 AC: 249

ESP6500AA AF: 0.0188 AC: 83

ESP6500EA AF: 0.0686 AC: 590

ExAC AF: 0.0930 AC: 11295

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.099
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.49	.;T;T
MetaRNN	Benign	0.0040	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.058
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.032
MutPred		0.19		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MPC		0.038
ClinPred		0.0068	T
GERP RS		4.6
Varity_R		0.11
gMVP		0.28

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: rs2305204; hg19: chr10-118364967; COSMIC: COSV62610794; COSMIC: COSV62610794;