NM_080476.5:c.318+1146A>C

Variant names:

• chr20-34643018-T-G
• rs6087612
• NM_080476.5:c.318+1146A>C

Variant summary

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

The NM_080476.5(PIGU):​c.318+1146A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,756 control chromosomes in the GnomAD database, including 12,076 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 0.39 (12076 hom., cov: 29)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 8 publications found

Genes affected

PIGU (HGNC:15791): (phosphatidylinositol glycan anchor biosynthesis class U) The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Cdc91, a predicted integral membrane protein that may function in cell division control. The protein encoded by this gene is the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins. [provided by RefSeq, Jul 2008]

PIGU Gene-Disease associations (from GenCC):

• glycosylphosphatidylinositol biosynthesis defect 21

  Inheritance: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.318+1146A>C		intron_variant	Intron 4 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.318+1146A>C		intron_variant	Intron 4 of 10		XP_016883153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.318+1146A>C		intron_variant	Intron 4 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.258+1146A>C		intron_variant	Intron 3 of 10	1		ENSP00000363953.2
PIGU	ENST00000628281.2	n.284+1146A>C		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59502 AN: 151638 Hom.: 12053 Cov.: 29

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.393 AC: 59570 AN: 151756 Hom.: 12076 Cov.: 29 AF XY: 0.392 AC XY: 29038 AN XY: 74160

African (AFR) AF: 0.382 AC: 15780 AN: 41354

American (AMR) AF: 0.558 AC: 8484 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1254 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2189 AN: 5154

South Asian (SAS) AF: 0.252 AC: 1210 AN: 4810

European-Finnish (FIN) AF: 0.326 AC: 3438 AN: 10534

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25743 AN: 67940

Other (OTH) AF: 0.423 AC: 885 AN: 2094

Alfa AF: 0.391 Hom.: 2260

Bravo AF: 0.416

Asia WGS AF: 0.347 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.62
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6087612; hg19: chr20-33230822;