10-116443118-C-G

Variant names:

• chr10-116443118-C-G
• rs954954313
• NM_001011709.3:c.268C>G

Variant summary

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

The NM_001011709.3(PNLIPRP3):​c.268C>G​(p.Arg90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R90C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNLIPRP3 NM_001011709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629
• Publications: 0 publications found

Genes affected

PNLIPRP3 (HGNC:23492): (pancreatic lipase related protein 3) Predicted to enable triglyceride lipase activity. Predicted to be involved in lipid catabolic process. Predicted to be active in extracellular space. [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, 0.934

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP3	NM_001011709.3	MANE Select	c.268C>G	p.Arg90Gly	missense	Exon 3 of 12	NP_001011709.2	Q17RR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP3	ENST00000369230.4	TSL:1 MANE Select	c.268C>G	p.Arg90Gly	missense	Exon 3 of 12	ENSP00000358232.3	Q17RR3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.63
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.75	P
Vest4		0.69
MutPred		0.74		Loss of MoRF binding (P = 0.007)
MVP		0.65
MPC		0.24
ClinPred		0.81	D
GERP RS		2.8
Varity_R		0.64
gMVP		0.65
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs954954313; hg19: chr10-118202630;