rs2378249

Variant names:

• chr20-34630286-G-A
• rs2378249
• NM_080476.5:c.529+4329C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-34630286-G-A
• chr20-34630286-G-C

Variant summary

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

The NM_080476.5(PIGU):​c.529+4329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,064 control chromosomes in the GnomAD database, including 54,798 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 0.85 (54798 hom., cov: 30)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 36 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.529+4329C>T		intron_variant	Intron 6 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.529+4329C>T		intron_variant	Intron 6 of 10		XP_016883153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.529+4329C>T		intron_variant	Intron 6 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.469+4329C>T		intron_variant	Intron 5 of 10	1		ENSP00000363953.2
PIGU	ENST00000480175.1	n.89+4329C>T		intron_variant	Intron 1 of 3	3
PIGU	ENST00000628281.2	n.495+4329C>T		intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128743 AN: 151946 Hom.: 54740 Cov.: 30

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.847 AC: 128862 AN: 152064 Hom.: 54798 Cov.: 30 AF XY: 0.849 AC XY: 63084 AN XY: 74334

African (AFR) AF: 0.837 AC: 34692 AN: 41472

American (AMR) AF: 0.916 AC: 13985 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4237 AN: 5164

South Asian (SAS) AF: 0.671 AC: 3229 AN: 4812

European-Finnish (FIN) AF: 0.884 AC: 9355 AN: 10586

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57189 AN: 67976

Other (OTH) AF: 0.875 AC: 1842 AN: 2106

Alfa AF: 0.845 Hom.: 48455

Bravo AF: 0.855

Asia WGS AF: 0.760 AC: 2641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.21
PhyloP100		-0.10
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: rs2378249; hg19: chr20-33218090; COSMIC: COSV54166315;