chr20-34641259-T-C

Variant names:

• chr20-34641259-T-C
• rs7269596
• NM_080476.5:c.318+2905A>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.318+2905A>G 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 151,940 control chromosomes in the GnomAD database, including 11,965 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 (11965 hom., cov: 31)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.318+2905A>G		intron_variant	Intron 4 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.318+2905A>G		intron_variant	Intron 4 of 10		XP_016883153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.318+2905A>G		intron_variant	Intron 4 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.258+2905A>G		intron_variant	Intron 3 of 10	1		ENSP00000363953.2
PIGU	ENST00000628281.2	n.284+2905A>G		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59295 AN: 151822 Hom.: 11942 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.391 AC: 59357 AN: 151940 Hom.: 11965 Cov.: 31 AF XY: 0.390 AC XY: 28931 AN XY: 74276

African (AFR) AF: 0.376 AC: 15572 AN: 41414

American (AMR) AF: 0.556 AC: 8495 AN: 15266

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

East Asian (EAS) AF: 0.424 AC: 2189 AN: 5166

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4816

European-Finnish (FIN) AF: 0.326 AC: 3450 AN: 10570

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25733 AN: 67930

Other (OTH) AF: 0.422 AC: 886 AN: 2102

Alfa AF: 0.418 Hom.: 3809

Bravo AF: 0.414

Asia WGS AF: 0.341 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.25
PhyloP100		0.50
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: rs7269596; hg19: chr20-33229063;