6-32155030-A-T

Variant names:

• chr6-32155030-A-T
• NM_005155.7:c.184A>T

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.184A>T​(p.Thr62Ser) variant causes a missense, splice region 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. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPT2 NM_005155.7 missense, splice_region
• Scores: Splicing: ADA: 0.03658
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• 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=0.19923857).

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.184A>T	p.Thr62Ser	missense splice_region	Exon 3 of 9	NP_005146.4
	PPT2	NM_138717.3		c.202A>T	p.Thr68Ser	missense splice_region	Exon 3 of 9	NP_619731.2	Q9UMR5-3
	PPT2	NM_001204103.2		c.184A>T	p.Thr62Ser	missense splice_region	Exon 3 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.184A>T	p.Thr62Ser	missense splice_region	Exon 3 of 9	ENSP00000320528.6	Q9UMR5-1
	PPT2	ENST00000361568.6	TSL:1	c.202A>T	p.Thr68Ser	missense splice_region	Exon 3 of 9	ENSP00000354608.2	Q9UMR5-3
	PPT2	ENST00000375137.6	TSL:1	c.184A>T	p.Thr62Ser	missense splice_region	Exon 3 of 9	ENSP00000364279.2	Q9UMR5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	0.0041	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.50	N
PhyloP100		3.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.36	N
REVEL	Uncertain	0.36
Sift	Benign	0.66	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.097
MutPred		0.53		Gain of disorder (P = 0.0907)
MVP		0.29
MPC		0.70
ClinPred		0.76	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.20
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.037
dbscSNV1_RF	Benign	0.18
SpliceAI score (max)		0.090		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

hg19: chr6-32122807;