rs2378199

Variant names:

• chr20-34598676-T-C
• rs2378199
• NM_080476.5:c.628-10069A>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.628-10069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,220 control chromosomes in the GnomAD database, including 52,946 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 (52946 hom., cov: 32)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 15 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 (AMR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.628-10069A>G		intron_variant	Intron 7 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.628-10069A>G		intron_variant	Intron 7 of 10		XP_016883153.1
PIGU	XM_011528542.2	c.-22+4454A>G		intron_variant	Intron 1 of 5		XP_011526844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.628-10069A>G		intron_variant	Intron 7 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.568-10069A>G		intron_variant	Intron 6 of 10	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.53-10069A>G		intron_variant	Intron 1 of 5	3		ENSP00000395755.1
PIGU	ENST00000480175.1	n.90-10069A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126526 AN: 152102 Hom.: 52891 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.832 AC: 126644 AN: 152220 Hom.: 52946 Cov.: 32 AF XY: 0.834 AC XY: 62066 AN XY: 74432

African (AFR) AF: 0.783 AC: 32496 AN: 41498

American (AMR) AF: 0.910 AC: 13922 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4244 AN: 5176

South Asian (SAS) AF: 0.669 AC: 3227 AN: 4822

European-Finnish (FIN) AF: 0.883 AC: 9371 AN: 10608

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

European-Non Finnish (NFE) AF: 0.841 AC: 57223 AN: 68032

Other (OTH) AF: 0.863 AC: 1825 AN: 2114

Alfa AF: 0.831 Hom.: 26983

Bravo AF: 0.838

Asia WGS AF: 0.759 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.48
DANN	Benign	0.67
PhyloP100		-2.7
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: rs2378199; hg19: chr20-33186480;