rs6088536

Variant names:

• chr20-34601302-T-C
• rs6088536
• NM_080476.5:c.628-12695A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-34601302-T-C
• chr20-34601302-T-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.628-12695A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,944 control chromosomes in the GnomAD database, including 15,149 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 (15149 hom., cov: 31)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 9 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: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGU	NM_080476.5	MANE Select	c.628-12695A>G		intron	N/A	NP_536724.1	Q9H490-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGU	ENST00000217446.8	TSL:1 MANE Select	c.628-12695A>G		intron	N/A	ENSP00000217446.3	Q9H490-1
	PIGU	ENST00000374820.6	TSL:1	c.568-12695A>G		intron	N/A	ENSP00000363953.2	Q9H490-2
	PIGU	ENST00000940070.1		c.619-12695A>G		intron	N/A	ENSP00000610129.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66500 AN: 151826 Hom.: 15142 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.438 AC: 66537 AN: 151944 Hom.: 15149 Cov.: 31 AF XY: 0.440 AC XY: 32674 AN XY: 74238

African (AFR) AF: 0.332 AC: 13763 AN: 41442

American (AMR) AF: 0.363 AC: 5529 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3472

East Asian (EAS) AF: 0.396 AC: 2044 AN: 5166

South Asian (SAS) AF: 0.421 AC: 2027 AN: 4818

European-Finnish (FIN) AF: 0.573 AC: 6030 AN: 10530

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

European-Non Finnish (NFE) AF: 0.494 AC: 33579 AN: 67946

Other (OTH) AF: 0.448 AC: 947 AN: 2112

Alfa AF: 0.450 Hom.: 2685

Bravo AF: 0.419

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.8
DANN	Benign	0.72
PhyloP100		1.9
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: rs6088536; hg19: chr20-33189106;