rs3130283

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-32170768-A-C
• chr6-32170768-A-G
• chr6-32170768-A-T

Variant summary

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

The ENST00000422437.5(PPT2-EGFL8):​n.*2039A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,218,050 control chromosomes in the GnomAD database, including 466,631 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 0.90 (61794 hom., cov: 30)
  • Exomes 𝑓: 0.87 (404837 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136805 AN: 151980 Hom.: 61732 Cov.: 30

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.915

GnomAD4 exome AF: 0.870 AC: 927714 AN: 1065952 Hom.: 404837 Cov.: 15 AF XY: 0.872 AC XY: 470879 AN XY: 539968

African (AFR) AF: 0.964 AC: 25240 AN: 26192

American (AMR) AF: 0.939 AC: 39663 AN: 42220

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 19054 AN: 20858

East Asian (EAS) AF: 0.906 AC: 34128 AN: 37688

South Asian (SAS) AF: 0.922 AC: 65670 AN: 71216

European-Finnish (FIN) AF: 0.869 AC: 32463 AN: 37370

Middle Eastern (MID) AF: 0.900 AC: 3205 AN: 3560

European-Non Finnish (NFE) AF: 0.856 AC: 667091 AN: 779656

Other (OTH) AF: 0.873 AC: 41200 AN: 47192

GnomAD4 genome AF: 0.900 AC: 136927 AN: 152098 Hom.: 61794 Cov.: 30 AF XY: 0.902 AC XY: 67033 AN XY: 74340

African (AFR) AF: 0.958 AC: 39758 AN: 41498

American (AMR) AF: 0.921 AC: 14082 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3173 AN: 3466

East Asian (EAS) AF: 0.929 AC: 4784 AN: 5148

South Asian (SAS) AF: 0.913 AC: 4408 AN: 4826

European-Finnish (FIN) AF: 0.884 AC: 9367 AN: 10598

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58301 AN: 67958

Other (OTH) AF: 0.917 AC: 1937 AN: 2112

Alfa AF: 0.879 Hom.: 154292

Bravo AF: 0.908

Asia WGS AF: 0.935 AC: 3252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.81
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV61247052; COSMIC: COSV61247052;