chr20-34560887-CT-C

Variant names:

• chr20-34560887-CT-C
• NM_080476.5:c.1286delA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_080476.5(PIGU):​c.1286delA​(p.Glu429GlyfsTer60) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIGU NM_080476.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.92

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-34560887-CT-C is Pathogenic according to our data. Variant chr20-34560887-CT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1696481.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.1286delA	p.Glu429GlyfsTer60	frameshift_variant	Exon 12 of 12	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.1142delA	p.Glu381GlyfsTer60	frameshift_variant	Exon 11 of 11		XP_016883153.1
PIGU	XM_011528542.2	c.638delA	p.Glu213GlyfsTer60	frameshift_variant	Exon 6 of 6		XP_011526844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.1286delA	p.Glu429GlyfsTer60	frameshift_variant	Exon 12 of 12	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.1226delA	p.Glu409GlyfsTer7	frameshift_variant	Exon 11 of 11	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.*15delA		downstream_gene_variant		3		ENSP00000395755.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glycosylphosphatidylinositol biosynthesis defect 21 Pathogenic:1

Jun 23, 2021

New York Genome Center

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33148691;