chr20-34576473-T-C

Position:

• chr20-34576473-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080476.5(PIGU):​c.1052-1227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,078 control chromosomes in the GnomAD database, including 53,020 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 (53020 hom., cov: 30)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGU	NM_080476.5	c.1052-1227A>G		intron_variant		ENST00000217446.8
PIGU	XM_011528542.2	c.404-1227A>G		intron_variant
PIGU	XM_017027664.2	c.908-1227A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGU	ENST00000217446.8	c.1052-1227A>G		intron_variant		1	NM_080476.5	P1
PIGU	ENST00000374820.6	c.992-1227A>G		intron_variant		1
PIGU	ENST00000438215.1	c.290-1227A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126549 AN: 151960 Hom.: 52965 Cov.: 30

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.833 AC: 126667 AN: 152078 Hom.: 53020 Cov.: 30 AF XY: 0.835 AC XY: 62039 AN XY: 74334

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.867

Alfa AF: 0.859 Hom.: 17326

Bravo AF: 0.839

Asia WGS AF: 0.756 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.034
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2889849; hg19: chr20-33164277;