rs6142210

Variant names:

• chr20-34635208-C-T
• rs6142210
• NM_080476.5:c.429-493G>A

Variant summary

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

The NM_080476.5(PIGU):​c.429-493G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,076 control chromosomes in the GnomAD database, including 12,005 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 0.39 (12005 hom., cov: 33)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 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.429-493G>A		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.429-493G>A		intron	N/A	ENSP00000217446.3	Q9H490-1
	PIGU	ENST00000374820.6	TSL:1	c.369-493G>A		intron	N/A	ENSP00000363953.2	Q9H490-2
	PIGU	ENST00000940070.1		c.420-493G>A		intron	N/A	ENSP00000610129.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59413 AN: 151958 Hom.: 11982 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.391 AC: 59475 AN: 152076 Hom.: 12005 Cov.: 33 AF XY: 0.390 AC XY: 29006 AN XY: 74350

African (AFR) AF: 0.376 AC: 15616 AN: 41480

American (AMR) AF: 0.557 AC: 8522 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1250 AN: 3472

East Asian (EAS) AF: 0.425 AC: 2200 AN: 5178

South Asian (SAS) AF: 0.248 AC: 1197 AN: 4822

European-Finnish (FIN) AF: 0.327 AC: 3463 AN: 10588

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25748 AN: 67934

Other (OTH) AF: 0.422 AC: 894 AN: 2116

Alfa AF: 0.432 Hom.: 4532

Bravo AF: 0.414

Asia WGS AF: 0.341 AC: 1182 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	3.3
DANN	Benign	0.49
PhyloP100		0.17
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: rs6142210; hg19: chr20-33223012;