NM_080476.5:c.1149C>G

Variant names:

• chr20-34575149-G-C
• NM_080476.5:c.1149C>G

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PS1 PM2 PP3_Strong

The NM_080476.5(PIGU):​c.1149C>G​(p.Asn383Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in Lovd.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PIGU NM_080476.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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 Pathogenic. Variant got 10 ACMG points.

• PS1: Transcript NM_080476.5 (PIGU) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.1149C>G	p.Asn383Lys	missense_variant	Exon 11 of 12	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.1005C>G	p.Asn335Lys	missense_variant	Exon 10 of 11		XP_016883153.1
PIGU	XM_011528542.2	c.501C>G	p.Asn167Lys	missense_variant	Exon 5 of 6		XP_011526844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGU	ENST00000217446.8	c.1149C>G	p.Asn383Lys	missense_variant	Exon 11 of 12	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.1089C>G	p.Asn363Lys	missense_variant	Exon 10 of 11	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.387C>G	p.Asn129Lys	missense_variant	Exon 5 of 6	3		ENSP00000395755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;.;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.070	D
MutationAssessor	Pathogenic	3.5	M;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.97
MutPred		0.96		Gain of ubiquitination at N383 (P = 0.03);.;.;
MVP		0.52
MPC		0.54
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.90

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: chr20-33162953;