NM_005155.7:c.343C>A

Variant names:

• chr6-32155693-C-A
• NM_005155.7:c.343C>A
• PPT2 p.Leu115Ile

Variant summary

Our verdict is

Uncertain significance

+3 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_005155.7(PPT2):​c.343C>A​(p.Leu115Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PPT2 NM_005155.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

Genes affected

PPT2 (HGNC:9326): (palmitoyl-protein thioesterase 2) This gene encodes a member of the palmitoyl-protein thioesterase family. The encoded glycosylated lysosomal protein has palmitoyl-CoA hydrolase activity in vitro, but does not hydrolyze palmitate from cysteine residues in proteins. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream EGFL8 (EGF-like-domain, multiple 8) gene. [provided by RefSeq, Feb 2011]

PPT2-EGFL8 (HGNC:48343): (PPT2-EGFL8 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring PPT2 (palmitoyl-protein thioesterase 2) and EGFL8 (EGF-like-domain, multiple 8) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: REVEL computational evidence supports a deleterious effect, 0.738

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005155.7. 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
	PPT2	NM_005155.7	MANE Select	c.343C>A	p.Leu115Ile	missense	Exon 4 of 9	NP_005146.4
	PPT2	NM_138717.3		c.361C>A	p.Leu121Ile	missense	Exon 4 of 9	NP_619731.2	Q9UMR5-3
	PPT2	NM_001204103.2		c.343C>A	p.Leu115Ile	missense	Exon 4 of 9	NP_001191032.1	A0A1U9X8D2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPT2	ENST00000324816.11	TSL:1 MANE Select	c.343C>A	p.Leu115Ile	missense	Exon 4 of 9	ENSP00000320528.6	Q9UMR5-1
	PPT2	ENST00000361568.6	TSL:1	c.361C>A	p.Leu121Ile	missense	Exon 4 of 9	ENSP00000354608.2	Q9UMR5-3
	PPT2	ENST00000375137.6	TSL:1	c.343C>A	p.Leu115Ile	missense	Exon 4 of 9	ENSP00000364279.2	Q9UMR5-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.5	N
REVEL	Pathogenic	0.74
Sift	Benign	0.070	T
Sift4G	Benign	0.12	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.70
Mutation Taster		=58/42	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-32123470;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline