rs4911158

Variant names:

• chr20-34651708-T-C
• rs4911158
• NM_080476.5:c.195+5472A>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.195+5472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,984 control chromosomes in the GnomAD database, including 13,665 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 0.42 (13665 hom., cov: 31)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.557 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.195+5472A>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.195+5472A>G		intron	N/A	ENSP00000217446.3
	PIGU	ENST00000374820.6	TSL:1	c.195+5472A>G		intron	N/A	ENSP00000363953.2
	PIGU	ENST00000462389.1	TSL:2	n.200+5472A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63251 AN: 151866 Hom.: 13637 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.417 AC: 63329 AN: 151984 Hom.: 13665 Cov.: 31 AF XY: 0.415 AC XY: 30824 AN XY: 74264

African (AFR) AF: 0.465 AC: 19294 AN: 41448

American (AMR) AF: 0.567 AC: 8645 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.423 AC: 2184 AN: 5160

South Asian (SAS) AF: 0.252 AC: 1216 AN: 4824

European-Finnish (FIN) AF: 0.326 AC: 3445 AN: 10562

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25775 AN: 67954

Other (OTH) AF: 0.439 AC: 926 AN: 2110

Alfa AF: 0.421 Hom.: 6449

Bravo AF: 0.443

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.45
PhyloP100		-0.77
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: rs4911158; hg19: chr20-33239512;