chr6-32168101-G-C

Variant names:

• chr6-32168101-G-C
• rs205000
• ENST00000422437.5:n.*943G>C

Variant summary

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

The ENST00000422437.5(PPT2-EGFL8):​n.*943G>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 0.0297 in 862,106 control chromosomes in the GnomAD database, including 921 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 0.036 (182 hom., cov: 33)
  • Exomes 𝑓: 0.028 (739 hom.)
• Consequence: PPT2-EGFL8 ENST00000422437.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 19 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]

EGFL8 (HGNC:13944): (EGF like domain multiple 8) Predicted to enable signaling receptor binding activity. Predicted to be involved in anatomical structure development. Predicted to act upstream of or within in utero embryonic development. Predicted to be active in cell surface and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL8	NM_030652.4	c.*145G>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000333845.11	NP_085155.1
AGPAT1	NM_006411.4	c.*1175C>G		downstream_gene_variant		ENST00000375107.8	NP_006402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPT2-EGFL8	ENST00000422437.5	n.*943G>C		non_coding_transcript_exon_variant	Exon 17 of 21	5		ENSP00000457534.1
EGFL8	ENST00000333845.11	c.*145G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_030652.4	ENSP00000333380.6
PPT2-EGFL8	ENST00000422437.5	n.*943G>C		3_prime_UTR_variant	Exon 17 of 21	5		ENSP00000457534.1
AGPAT1	ENST00000375107.8	c.*1175C>G		downstream_gene_variant		1	NM_006411.4	ENSP00000364248.3

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5455 AN: 152212 Hom.: 184 Cov.: 33

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0284 AC: 20126 AN: 709774 Hom.: 739 Cov.: 9 AF XY: 0.0311 AC XY: 11363 AN XY: 365102

African (AFR) AF: 0.0602 AC: 1043 AN: 17320

American (AMR) AF: 0.0248 AC: 646 AN: 26068

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 240 AN: 16406

East Asian (EAS) AF: 0.109 AC: 3620 AN: 33068

South Asian (SAS) AF: 0.104 AC: 5746 AN: 55250

European-Finnish (FIN) AF: 0.00487 AC: 229 AN: 47068

Middle Eastern (MID) AF: 0.0246 AC: 98 AN: 3986

European-Non Finnish (NFE) AF: 0.0156 AC: 7445 AN: 476200

Other (OTH) AF: 0.0308 AC: 1059 AN: 34408

GnomAD4 genome AF: 0.0359 AC: 5465 AN: 152332 Hom.: 182 Cov.: 33 AF XY: 0.0364 AC XY: 2712 AN XY: 74486

African (AFR) AF: 0.0623 AC: 2589 AN: 41564

American (AMR) AF: 0.0354 AC: 542 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 46 AN: 3472

East Asian (EAS) AF: 0.111 AC: 574 AN: 5186

South Asian (SAS) AF: 0.0968 AC: 467 AN: 4826

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10628

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0161 AC: 1096 AN: 68038

Other (OTH) AF: 0.0474 AC: 100 AN: 2110

Alfa AF: 0.0191 Hom.: 50

Bravo AF: 0.0377

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.73
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs205000; hg19: chr6-32135878;