rs764597

Variant names:

• chr20-34573421-G-A
• rs764597
• NM_080476.5:c.1194+1683C>T

Variant summary

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

The NM_080476.5(PIGU):​c.1194+1683C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,010 control chromosomes in the GnomAD database, including 15,274 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 0.44 (15274 hom., cov: 31)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.1194+1683C>T		intron_variant	Intron 11 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.1050+1683C>T		intron_variant	Intron 10 of 10		XP_016883153.1
PIGU	XM_011528542.2	c.546+1683C>T		intron_variant	Intron 5 of 5		XP_011526844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.1194+1683C>T		intron_variant	Intron 11 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.1134+1683C>T		intron_variant	Intron 10 of 10	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.432+1683C>T		intron_variant	Intron 5 of 5	3		ENSP00000395755.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66762 AN: 151890 Hom.: 15267 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.439 AC: 66800 AN: 152010 Hom.: 15274 Cov.: 31 AF XY: 0.441 AC XY: 32797 AN XY: 74294

African (AFR) AF: 0.332 AC: 13775 AN: 41448

American (AMR) AF: 0.364 AC: 5555 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2032 AN: 3468

East Asian (EAS) AF: 0.396 AC: 2043 AN: 5158

South Asian (SAS) AF: 0.414 AC: 1990 AN: 4812

European-Finnish (FIN) AF: 0.575 AC: 6078 AN: 10570

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33802 AN: 67964

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.446 Hom.: 5263

Bravo AF: 0.420

Asia WGS AF: 0.403 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.22
PhyloP100		-0.94
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: rs764597; hg19: chr20-33161225;