rs3134950

Variant names:

• chr6-32159700-C-A
• rs3134950
• NM_005155.7:c.710+1776C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32159700-C-A
• chr6-32159700-C-G
• chr6-32159700-C-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.710+1776C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 150,720 control chromosomes in the GnomAD database, including 31,115 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 0.64 (31115 hom., cov: 28)
• Consequence: PPT2 NM_005155.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 35 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 (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPT2	NM_005155.7	c.710+1776C>A		intron_variant	Intron 7 of 8	ENST00000324816.11	NP_005146.4
PPT2	NM_138717.3	c.728+1776C>A		intron_variant	Intron 7 of 8		NP_619731.2
PPT2	NM_001204103.2	c.710+1776C>A		intron_variant	Intron 7 of 8		NP_001191032.1
PPT2-EGFL8	NR_037861.1	n.1124+1776C>A		intron_variant	Intron 7 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPT2	ENST00000324816.11	c.710+1776C>A		intron_variant	Intron 7 of 8	1	NM_005155.7	ENSP00000320528.6
PPT2-EGFL8	ENST00000422437.5	n.710+1776C>A		intron_variant	Intron 7 of 20	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 96496 AN: 150622 Hom.: 31099 Cov.: 28

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.641 AC: 96563 AN: 150720 Hom.: 31115 Cov.: 28 AF XY: 0.639 AC XY: 47015 AN XY: 73570

African (AFR) AF: 0.677 AC: 27787 AN: 41050

American (AMR) AF: 0.630 AC: 9539 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2583 AN: 3466

East Asian (EAS) AF: 0.585 AC: 3003 AN: 5130

South Asian (SAS) AF: 0.684 AC: 3279 AN: 4794

European-Finnish (FIN) AF: 0.572 AC: 5789 AN: 10128

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42282 AN: 67714

Other (OTH) AF: 0.686 AC: 1439 AN: 2098

Alfa AF: 0.644 Hom.: 46784

Bravo AF: 0.648

Asia WGS AF: 0.666 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.083
DANN	Benign	0.66
PhyloP100		-1.1
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: rs3134950; hg19: chr6-32127477;