6-32156647-G-T

Variant names:

• chr6-32156647-G-T
• rs10947233
• NM_005155.7:c.541+669G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005155.7(PPT2):​c.541+669G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 152,180 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.036 (205 hom., cov: 31)
• Consequence: PPT2 NM_005155.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 24 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPT2	NM_005155.7	c.541+669G>T		intron_variant	Intron 5 of 8	ENST00000324816.11	NP_005146.4
PPT2	NM_138717.3	c.559+669G>T		intron_variant	Intron 5 of 8		NP_619731.2
PPT2	NM_001204103.2	c.541+669G>T		intron_variant	Intron 5 of 8		NP_001191032.1
PPT2-EGFL8	NR_037861.1	n.955+669G>T		intron_variant	Intron 5 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPT2	ENST00000324816.11	c.541+669G>T		intron_variant	Intron 5 of 8	1	NM_005155.7	ENSP00000320528.6
PPT2-EGFL8	ENST00000422437.5	n.541+669G>T		intron_variant	Intron 5 of 20	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5469 AN: 152062 Hom.: 205 Cov.: 31

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.00977

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0359 AC: 5462 AN: 152180 Hom.: 205 Cov.: 31 AF XY: 0.0366 AC XY: 2721 AN XY: 74400

African (AFR) AF: 0.0154 AC: 641 AN: 41506

American (AMR) AF: 0.00975 AC: 149 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.208 AC: 1077 AN: 5180

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4820

European-Finnish (FIN) AF: 0.0439 AC: 465 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0402 AC: 2732 AN: 68006

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0398 Hom.: 529

Bravo AF: 0.0334

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs10947233; hg19: chr6-32124424;