20-34675229-T-C

Variant names:

• chr20-34675229-T-C
• rs6087616
• NM_080476.5:c.130+1727A>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.130+1727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.43 (11932 hom., cov: 18)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.130+1727A>G		intron_variant	Intron 1 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.130+1727A>G		intron_variant	Intron 1 of 10		XP_016883153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.130+1727A>G		intron_variant	Intron 1 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.130+1727A>G		intron_variant	Intron 1 of 10	1		ENSP00000363953.2
PIGU	ENST00000462389.1	n.135+1727A>G		intron_variant	Intron 1 of 3	2
PIGU	ENST00000628281.2	n.97-17985A>G		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.435 AC: 55984 AN: 128788 Hom.: 11917 Cov.: 18

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.435 AC: 56022 AN: 128818 Hom.: 11932 Cov.: 18 AF XY: 0.442 AC XY: 26599 AN XY: 60204

African (AFR) AF: 0.487 AC: 16462 AN: 33780

American (AMR) AF: 0.619 AC: 7262 AN: 11726

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1222 AN: 3332

East Asian (EAS) AF: 0.441 AC: 1954 AN: 4432

South Asian (SAS) AF: 0.260 AC: 1045 AN: 4016

European-Finnish (FIN) AF: 0.408 AC: 2143 AN: 5250

Middle Eastern (MID) AF: 0.505 AC: 105 AN: 208

European-Non Finnish (NFE) AF: 0.387 AC: 24590 AN: 63518

Other (OTH) AF: 0.468 AC: 806 AN: 1722

Alfa AF: 0.215 Hom.: 445

Bravo AF: 0.441

Asia WGS AF: 0.348 AC: 1207 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.35
PhyloP100		-0.30
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: rs6087616; hg19: chr20-33263033;