6-32170768-A-T

Variant names:

• chr6-32170768-A-T
• rs3130283
• ENST00000422437.5:n.*2039A>T

Variant summary

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

The ENST00000422437.5(PPT2-EGFL8):​n.*2039A>T variant causes a non coding transcript exon 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: 30)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPT2-EGFL8 ENST00000422437.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 47 publications found

Genes affected

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]

AGPAT1 (HGNC:324): (1-acylglycerol-3-phosphate O-acyltransferase 1) This gene encodes an enzyme that converts lysophosphatidic acid (LPA) into phosphatidic acid (PA). LPA and PA are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. This enzyme localizes to the endoplasmic reticulum. This gene is located in the class III region of the human major histocompatibility complex. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPAT1	NM_006411.4	c.335-168T>A		intron_variant	Intron 3 of 6	ENST00000375107.8	NP_006402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPT2-EGFL8	ENST00000422437.5	n.*2039A>T		non_coding_transcript_exon_variant	Exon 20 of 21	5		ENSP00000457534.1
PPT2-EGFL8	ENST00000422437.5	n.*2039A>T		3_prime_UTR_variant	Exon 20 of 21	5		ENSP00000457534.1
AGPAT1	ENST00000375107.8	c.335-168T>A		intron_variant	Intron 3 of 6	1	NM_006411.4	ENSP00000364248.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000187 AC: 2 AN: 1066962 Hom.: 0 Cov.: 15 AF XY: 0.00000185 AC XY: 1 AN XY: 540480

African (AFR) AF: 0.00 AC: 0 AN: 26194

American (AMR) AF: 0.00 AC: 0 AN: 42228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20862

East Asian (EAS) AF: 0.00 AC: 0 AN: 37694

South Asian (SAS) AF: 0.00 AC: 0 AN: 71228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3566

European-Non Finnish (NFE) AF: 0.00000256 AC: 2 AN: 780582

Other (OTH) AF: 0.00 AC: 0 AN: 47228

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 154292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		-0.87

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: rs3130283; hg19: chr6-32138545;