rs3134603

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-32158225-A-C
• chr6-32158225-A-G
• chr6-32158225-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005155.7(PPT2):​c.710+301A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPT2	NM_005155.7	c.710+301A>C		intron_variant	Intron 7 of 8	ENST00000324816.11	NP_005146.4
PPT2	NM_138717.3	c.728+301A>C		intron_variant	Intron 7 of 8		NP_619731.2
PPT2	NM_001204103.2	c.710+301A>C		intron_variant	Intron 7 of 8		NP_001191032.1
PPT2-EGFL8	NR_037861.1	n.1124+301A>C		intron_variant	Intron 7 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPT2	ENST00000324816.11	c.710+301A>C		intron_variant	Intron 7 of 8	1	NM_005155.7	ENSP00000320528.6
PPT2-EGFL8	ENST00000422437.5	n.710+301A>C		intron_variant	Intron 7 of 20	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 189702 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 96936

African (AFR) AF: 0.00 AC: 0 AN: 6074

American (AMR) AF: 0.00 AC: 0 AN: 7300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7156

East Asian (EAS) AF: 0.00 AC: 0 AN: 15786

South Asian (SAS) AF: 0.00 AC: 0 AN: 9296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 998

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 118908

Other (OTH) AF: 0.00 AC: 0 AN: 12716

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 173015

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.79
PhyloP100		-0.36

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;