chr10-116592536-T-G

Variant names:

• chr10-116592536-T-G
• rs1847658206
• NM_006229.4:c.325T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006229.4(PNLIPRP1):​c.325T>G​(p.Cys109Gly) 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. C109R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.325T>G	p.Cys109Gly	missense_variant	Exon 4 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.325T>G	p.Cys109Gly	missense_variant	Exon 4 of 13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.325T>G	p.Cys109Gly	missense_variant	Exon 4 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.325T>G	p.Cys109Gly	missense_variant	Exon 4 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.65	D;D;D;.;D;D;.
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T;.;T;T;T;T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Uncertain	2.5	.;M;M;.;.;.;.
PhyloP100		6.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-12	D;D;D;D;D;D;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0060	D;D;D;D;D;D;D
Sift4G	Uncertain	0.039	D;D;D;D;D;D;D
Polyphen		1.0	.;D;D;.;.;.;.
Vest4		0.85, 0.86
MutPred		0.68		Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);Loss of stability (P = 0.0143);
MVP		1.0
MPC		0.31
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.97
gMVP		0.54
Mutation Taster		=39/61	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1847658206; hg19: chr10-118352048;