chr10-116596232-C-G

Variant names:

• chr10-116596232-C-G
• rs200174051
• NM_006229.4:c.484C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006229.4(PNLIPRP1):​c.484C>G​(p.Pro162Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,612,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P162R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23884755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.484C>G	p.Pro162Ala	missense_variant	Exon 6 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.484C>G	p.Pro162Ala	missense_variant	Exon 6 of 13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.484C>G	p.Pro162Ala	missense_variant	Exon 6 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.484C>G	p.Pro162Ala	missense_variant	Exon 6 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000836 AC: 21 AN: 251266 AF XY: 0.0000884

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000147 AC: 215 AN: 1460176 Hom.: 0 Cov.: 30 AF XY: 0.000131 AC XY: 95 AN XY: 726554

African (AFR) AF: 0.0000299 AC: 1 AN: 33436

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000178 AC: 198 AN: 1110470

Other (OTH) AF: 0.000232 AC: 14 AN: 60340

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74354

African (AFR) AF: 0.0000965 AC: 4 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.000140

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	1.6
DANN	Benign	0.22
DEOGEN2	Uncertain	0.65	D;D;D;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.55	T;.;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	0.78	.;N;N;.;.
PhyloP100		0.87
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.1	D;D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.24	T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T
Polyphen		0.021	.;B;B;.;.
Vest4		0.28, 0.28
MVP		0.80
MPC		0.045
ClinPred		0.048	T
GERP RS		0.66
Varity_R		0.24
gMVP		0.59
Mutation Taster		=83/17	polymorphism

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: rs200174051; hg19: chr10-118355744;