chr10-116605455-G-C

Variant names:

• chr10-116605455-G-C
• rs2305204
• NM_006229.4:c.1242G>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.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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• 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]

LOC124902510 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.1242G>C	p.Glu414Asp	missense	Exon 12 of 13	NP_006220.1
	PNLIPRP1	NM_001303135.1		c.1242G>C	p.Glu414Asp	missense	Exon 12 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.1242G>C	p.Glu414Asp	missense	Exon 12 of 13	ENSP00000351695.4
	PNLIPRP1	ENST00000525820.5	TSL:1	n.3038G>C		non_coding_transcript_exon	Exon 11 of 12
	PNLIPRP1	ENST00000526223.5	TSL:1	n.3194G>C		non_coding_transcript_exon	Exon 11 of 12

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

GnomAD2 exomes AF: 0.0930 AC: 23354 AN: 251198 AF XY: 0.0944

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 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

African (AFR) AF: 0.0155 AC: 519 AN: 33434

American (AMR) AF: 0.0457 AC: 2042 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 2076 AN: 26074

East Asian (EAS) AF: 0.399 AC: 15802 AN: 39582

South Asian (SAS) AF: 0.102 AC: 8743 AN: 85898

European-Finnish (FIN) AF: 0.0667 AC: 3558 AN: 53372

Middle Eastern (MID) AF: 0.106 AC: 611 AN: 5760

European-Non Finnish (NFE) AF: 0.0645 AC: 71562 AN: 1109496

Other (OTH) AF: 0.0923 AC: 5564 AN: 60256

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

African (AFR) AF: 0.0157 AC: 652 AN: 41536

American (AMR) AF: 0.0506 AC: 774 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2101 AN: 5156

South Asian (SAS) AF: 0.121 AC: 581 AN: 4816

European-Finnish (FIN) AF: 0.0678 AC: 717 AN: 10580

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4499 AN: 68008

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

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 v4.9

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
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.099
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.47
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.058
Sift	Benign	0.41	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.032
MutPred		0.19		Gain of sheet (P = 0.0827)
MPC		0.038
ClinPred		0.0068	T
GERP RS		4.6
Varity_R		0.11
gMVP		0.28
Mutation Taster		=100/0	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: rs2305204; hg19: chr10-118364967; COSMIC: COSV62610794; COSMIC: COSV62610794;