chr6-32154686-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPT2	NM_005155.7	c.92C>A	p.Pro31His	missense_variant	Exon 2 of 9	ENST00000324816.11	NP_005146.4
PPT2	NM_138717.3	c.110C>A	p.Pro37His	missense_variant	Exon 2 of 9		NP_619731.2
PPT2	NM_001204103.2	c.92C>A	p.Pro31His	missense_variant	Exon 2 of 9		NP_001191032.1
PPT2-EGFL8	NR_037861.1	n.506C>A		non_coding_transcript_exon_variant	Exon 2 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPT2	ENST00000324816.11	c.92C>A	p.Pro31His	missense_variant	Exon 2 of 9	1	NM_005155.7	ENSP00000320528.6
PPT2-EGFL8	ENST00000422437.5	n.92C>A		non_coding_transcript_exon_variant	Exon 2 of 21	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;T;T;T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T;T;.;T;.;.;D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.90	.;.;L;L;L;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.096	T;T;T;T;T;T;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T
Polyphen		0.14	.;.;B;B;B;B;.
Vest4		0.13, 0.13
MutPred		0.29		Loss of glycosylation at P31 (P = 0.0449);.;Loss of glycosylation at P31 (P = 0.0449);Loss of glycosylation at P31 (P = 0.0449);Loss of glycosylation at P31 (P = 0.0449);Loss of glycosylation at P31 (P = 0.0449);Loss of glycosylation at P31 (P = 0.0449);
MVP		0.29
MPC		1.9
ClinPred		0.39	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.066
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs552013847; hg19: chr6-32122463;