10-116591902-A-T

Position:

• chr10-116591902-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006229.4(PNLIPRP1):​c.181A>T​(p.Asn61Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. N61D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.181A>T	p.Asn61Tyr	missense_variant	3/13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.181A>T	p.Asn61Tyr	missense_variant	3/13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.181A>T	p.Asn61Tyr	missense_variant	3/9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.181A>T	p.Asn61Tyr	missense_variant	3/13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D;D;D;.;D;D;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D;.;D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.0	.;M;M;.;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.0	D;D;D;D;D;D;D
REVEL	Uncertain	0.59
Sift	Benign	0.044	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;T;D
Polyphen		1.0	.;D;D;.;.;.;.
Vest4		0.51, 0.51
MutPred		0.51		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.99
MPC		0.28
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.60
gMVP		0.61

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: rs11197744; hg19: chr10-118351414;