20-34592348-T-C

Variant names:

• chr20-34592348-T-C
• rs17305573
• NM_080476.5:c.628-3741A>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.628-3741A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 139,998 control chromosomes in the GnomAD database, including 259 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 0.050 (259 hom., cov: 31)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 23 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080476.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGU	NM_080476.5	MANE Select	c.628-3741A>G		intron	N/A	NP_536724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGU	ENST00000217446.8	TSL:1 MANE Select	c.628-3741A>G		intron	N/A	ENSP00000217446.3
	PIGU	ENST00000374820.6	TSL:1	c.568-3741A>G		intron	N/A	ENSP00000363953.2
	PIGU	ENST00000438215.1	TSL:3	c.53-3741A>G		intron	N/A	ENSP00000395755.1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 6931 AN: 139900 Hom.: 259 Cov.: 31

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00463

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.000214

Gnomad SAS AF: 0.00736

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0110

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0495 AC: 6933 AN: 139998 Hom.: 259 Cov.: 31 AF XY: 0.0454 AC XY: 3081 AN XY: 67904

African (AFR) AF: 0.0161 AC: 600 AN: 37356

American (AMR) AF: 0.0322 AC: 454 AN: 14106

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 100 AN: 3314

East Asian (EAS) AF: 0.000215 AC: 1 AN: 4654

South Asian (SAS) AF: 0.00782 AC: 35 AN: 4474

European-Finnish (FIN) AF: 0.0209 AC: 184 AN: 8810

Middle Eastern (MID) AF: 0.0122 AC: 3 AN: 246

European-Non Finnish (NFE) AF: 0.0853 AC: 5480 AN: 64220

Other (OTH) AF: 0.0368 AC: 72 AN: 1954

Alfa AF: 0.0660 Hom.: 462

Bravo AF: 0.0455

Asia WGS AF: 0.00521 AC: 18 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.63
PhyloP100		-0.90
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: rs17305573; hg19: chr20-33180152;