6-32154686-C-A

Variant names:

• chr6-32154686-C-A
• rs552013847
• NM_005155.7:c.92C>A

Variant summary

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

The NM_005155.7(PPT2):​c.92C>A​(p.Pro31His) 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. 15/22 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. P31L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPT2 NM_005155.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1359232).

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.92C>A	p.Pro31His	missense	Exon 2 of 9	NP_005146.4
	PPT2	NM_138717.3		c.110C>A	p.Pro37His	missense	Exon 2 of 9	NP_619731.2	Q9UMR5-3
	PPT2	NM_001204103.2		c.92C>A	p.Pro31His	missense	Exon 2 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.92C>A	p.Pro31His	missense	Exon 2 of 9	ENSP00000320528.6	Q9UMR5-1
	PPT2	ENST00000361568.6	TSL:1	c.110C>A	p.Pro37His	missense	Exon 2 of 9	ENSP00000354608.2	Q9UMR5-3
	PPT2	ENST00000375137.6	TSL:1	c.92C>A	p.Pro31His	missense	Exon 2 of 9	ENSP00000364279.2	Q9UMR5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 245994 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.00023	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.077
Sift	Benign	0.096	T
Sift4G	Benign	0.15	T
Polyphen		0.14	B
Vest4		0.13
MutPred		0.29		Loss of glycosylation at P31 (P = 0.0449)
MVP		0.29
MPC		1.9
ClinPred		0.39	T
GERP RS		2.8
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.066
gMVP		0.22
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs552013847; hg19: chr6-32122463;