6-32158225-A-G

Variant names:

• chr6-32158225-A-G
• rs3134603
• NM_005155.7:c.710+301A>G

Variant summary

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

The NM_005155.7(PPT2):​c.710+301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 341,516 control chromosomes in the GnomAD database, including 132,436 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 0.89 (61043 hom., cov: 31)
  • Exomes 𝑓: 0.87 (71393 hom.)
• Consequence: PPT2 NM_005155.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 42 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPT2	NM_005155.7	MANE Select	c.710+301A>G		intron	N/A	NP_005146.4
	PPT2	NM_138717.3		c.728+301A>G		intron	N/A	NP_619731.2
	PPT2	NM_001204103.2		c.710+301A>G		intron	N/A	NP_001191032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPT2	ENST00000324816.11	TSL:1 MANE Select	c.710+301A>G		intron	N/A	ENSP00000320528.6
	PPT2	ENST00000361568.6	TSL:1	c.728+301A>G		intron	N/A	ENSP00000354608.2
	PPT2	ENST00000375137.6	TSL:1	c.710+301A>G		intron	N/A	ENSP00000364279.2

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135996 AN: 152094 Hom.: 60988 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.867 AC: 164165 AN: 189306 Hom.: 71393 Cov.: 2 AF XY: 0.867 AC XY: 83879 AN XY: 96744

African (AFR) AF: 0.957 AC: 5809 AN: 6070

American (AMR) AF: 0.903 AC: 6577 AN: 7280

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 6444 AN: 7148

East Asian (EAS) AF: 0.829 AC: 13053 AN: 15738

South Asian (SAS) AF: 0.848 AC: 7869 AN: 9276

European-Finnish (FIN) AF: 0.891 AC: 10179 AN: 11430

Middle Eastern (MID) AF: 0.837 AC: 830 AN: 992

European-Non Finnish (NFE) AF: 0.863 AC: 102445 AN: 118676

Other (OTH) AF: 0.863 AC: 10959 AN: 12696

GnomAD4 genome AF: 0.894 AC: 136107 AN: 152210 Hom.: 61043 Cov.: 31 AF XY: 0.894 AC XY: 66545 AN XY: 74426

African (AFR) AF: 0.955 AC: 39635 AN: 41500

American (AMR) AF: 0.906 AC: 13850 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3154 AN: 3470

East Asian (EAS) AF: 0.811 AC: 4202 AN: 5182

South Asian (SAS) AF: 0.826 AC: 3984 AN: 4822

European-Finnish (FIN) AF: 0.902 AC: 9569 AN: 10614

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58688 AN: 68010

Other (OTH) AF: 0.903 AC: 1908 AN: 2114

Alfa AF: 0.877 Hom.: 173015

Bravo AF: 0.901

Asia WGS AF: 0.816 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.81
PhyloP100		-0.36
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: rs3134603; hg19: chr6-32126002;