20-34576473-T-C

Variant names:

• chr20-34576473-T-C
• rs2889849
• NM_080476.5:c.1052-1227A>G

Variant summary

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

The NM_080476.5(PIGU):​c.1052-1227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,078 control chromosomes in the GnomAD database, including 53,020 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 0.83 (53020 hom., cov: 30)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 10 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.1052-1227A>G		intron_variant	Intron 10 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.908-1227A>G		intron_variant	Intron 9 of 10		XP_016883153.1
PIGU	XM_011528542.2	c.404-1227A>G		intron_variant	Intron 4 of 5		XP_011526844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.1052-1227A>G		intron_variant	Intron 10 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.992-1227A>G		intron_variant	Intron 9 of 10	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.290-1227A>G		intron_variant	Intron 4 of 5	3		ENSP00000395755.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126549 AN: 151960 Hom.: 52965 Cov.: 30

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.833 AC: 126667 AN: 152078 Hom.: 53020 Cov.: 30 AF XY: 0.835 AC XY: 62039 AN XY: 74334

African (AFR) AF: 0.787 AC: 32620 AN: 41466

American (AMR) AF: 0.912 AC: 13941 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3189 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4234 AN: 5160

South Asian (SAS) AF: 0.662 AC: 3186 AN: 4812

European-Finnish (FIN) AF: 0.883 AC: 9340 AN: 10582

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57186 AN: 67982

Other (OTH) AF: 0.867 AC: 1828 AN: 2108

Alfa AF: 0.861 Hom.: 19110

Bravo AF: 0.839

Asia WGS AF: 0.756 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.034
DANN	Benign	0.40
PhyloP100		-3.3
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: rs2889849; hg19: chr20-33164277;