10-116455726-A-C

Variant names:

• chr10-116455726-A-C
• rs368840270
• NM_001011709.3:c.461A>C

Variant summary

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

The NM_001011709.3(PNLIPRP3):​c.461A>C​(p.Lys154Thr) 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 benign outcome for this variant. 17/22 in silico tools predict a benign 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. K154I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PNLIPRP3 NM_001011709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10955423).

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.461A>C	p.Lys154Thr	missense	Exon 5 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.461A>C	p.Lys154Thr	missense	Exon 5 of 12	ENSP00000358232.3	Q17RR3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Benign	0.50	T
Sift4G	Benign	0.50	T
Polyphen		0.060	B
Vest4		0.33
MutPred		0.51		Loss of methylation at K154 (P = 0.0071)
MVP		0.60
MPC		0.051
ClinPred		0.18	T
GERP RS		3.6
Varity_R		0.091
gMVP		0.43
Mutation Taster		=97/3	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: rs368840270; hg19: chr10-118215238; COSMIC: COSV65048364;