10-116591812-A-C

Variant names:

• chr10-116591812-A-C
• rs573785414
• NM_006229.4:c.91A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006229.4(PNLIPRP1):​c.91A>C​(p.Thr31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.25
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11645371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.91A>C	p.Thr31Pro	missense_variant	Exon 3 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.91A>C	p.Thr31Pro	missense_variant	Exon 3 of 13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.91A>C	p.Thr31Pro	missense_variant	Exon 3 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.91A>C	p.Thr31Pro	missense_variant	Exon 3 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251028 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91A>C (p.T31P) alteration is located in exon 3 (coding exon 2) of the PNLIPRP1 gene. This alteration results from a A to C substitution at nucleotide position 91, causing the threonine (T) at amino acid position 31 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.38	T;T;T;.;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.52	T;.;T;T;T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.095	D
MutationAssessor	Benign	0.79	.;N;N;.;.;.;.
PhyloP100		-1.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.056	T;D;D;T;D;T;D
Sift4G	Benign	0.098	T;T;T;T;T;T;T
Polyphen		0.015	.;B;B;.;.;.;.
Vest4		0.24, 0.25
MutPred		0.31		Gain of disorder (P = 0.1109);Gain of disorder (P = 0.1109);Gain of disorder (P = 0.1109);Gain of disorder (P = 0.1109);Gain of disorder (P = 0.1109);Gain of disorder (P = 0.1109);Gain of disorder (P = 0.1109);
MVP		0.56
MPC		0.055
ClinPred		0.12	T
GERP RS		-11
Varity_R		0.43
gMVP		0.55
Mutation Taster		=100/0	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: rs573785414; hg19: chr10-118351324;