20-34583564-G-C

Variant names:

• chr20-34583564-G-C
• rs932542
• NM_080476.5:c.926+1873C>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.926+1873C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,262 control chromosomes in the GnomAD database, including 55,015 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 0.85 (55015 hom., cov: 33)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.926+1873C>G		intron_variant	Intron 9 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.783-1892C>G		intron_variant	Intron 8 of 10		XP_016883153.1
PIGU	XM_011528542.2	c.278+1873C>G		intron_variant	Intron 3 of 5		XP_011526844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.926+1873C>G		intron_variant	Intron 9 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.866+1873C>G		intron_variant	Intron 8 of 10	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.164+1873C>G		intron_variant	Intron 3 of 5	3		ENSP00000395755.1
PIGU	ENST00000480175.1	n.245-1892C>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.848 AC: 129083 AN: 152144 Hom.: 54957 Cov.: 33

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.849 AC: 129202 AN: 152262 Hom.: 55015 Cov.: 33 AF XY: 0.850 AC XY: 63257 AN XY: 74458

African (AFR) AF: 0.840 AC: 34901 AN: 41530

American (AMR) AF: 0.917 AC: 14030 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3191 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4237 AN: 5174

South Asian (SAS) AF: 0.670 AC: 3233 AN: 4826

European-Finnish (FIN) AF: 0.883 AC: 9382 AN: 10622

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

European-Non Finnish (NFE) AF: 0.841 AC: 57228 AN: 68016

Other (OTH) AF: 0.879 AC: 1859 AN: 2116

Alfa AF: 0.854 Hom.: 6920

Bravo AF: 0.857

Asia WGS AF: 0.760 AC: 2642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.74
PhyloP100		0.065
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: rs932542; hg19: chr20-33171368;