chr20-34604942-C-G

Variant names:

• chr20-34604942-C-G
• rs6141488
• NM_080476.5:c.627+11100G>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.627+11100G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,790 control chromosomes in the GnomAD database, including 10,359 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 0.36 (10359 hom., cov: 30)
• Consequence: PIGU NM_080476.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.627+11100G>C		intron_variant	Intron 7 of 11	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.627+11100G>C		intron_variant	Intron 7 of 10		XP_016883153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.627+11100G>C		intron_variant	Intron 7 of 11	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.567+11100G>C		intron_variant	Intron 6 of 10	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.52+11100G>C		intron_variant	Intron 1 of 5	3		ENSP00000395755.1
PIGU	ENST00000480175.1	n.90-16335G>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55056 AN: 151672 Hom.: 10336 Cov.: 30

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.363 AC: 55128 AN: 151790 Hom.: 10359 Cov.: 30 AF XY: 0.364 AC XY: 26963 AN XY: 74140

African (AFR) AF: 0.370 AC: 15336 AN: 41420

American (AMR) AF: 0.526 AC: 8004 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1150 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2180 AN: 5144

South Asian (SAS) AF: 0.245 AC: 1178 AN: 4802

European-Finnish (FIN) AF: 0.302 AC: 3170 AN: 10506

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22734 AN: 67926

Other (OTH) AF: 0.392 AC: 827 AN: 2112

Alfa AF: 0.342 Hom.: 1147

Bravo AF: 0.386

Asia WGS AF: 0.343 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		-0.23
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: rs6141488; hg19: chr20-33192746;