chr10-116596268-G-A

Variant names:

• chr10-116596268-G-A
• rs139392611
• NM_006229.4:c.520G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006229.4(PNLIPRP1):​c.520G>A​(p.Ala174Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A174P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.520G>A	p.Ala174Thr	missense_variant	Exon 6 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.520G>A	p.Ala174Thr	missense_variant	Exon 6 of 13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.520G>A	p.Ala174Thr	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.520G>A	p.Ala174Thr	missense_variant	Exon 6 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111894

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.86	D;D;D;.;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;.;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.3	.;H;H;.;.
PhyloP100		6.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.85, 0.85
MutPred		0.94		Gain of glycosylation at A174 (P = 0.0135);Gain of glycosylation at A174 (P = 0.0135);Gain of glycosylation at A174 (P = 0.0135);.;Gain of glycosylation at A174 (P = 0.0135);
MVP		0.98
MPC		0.29
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.90
gMVP		0.71
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139392611; hg19: chr10-118355780;