NM_080476.5:c.1278T>G

Variant names:

• chr20-34560896-A-C
• NM_080476.5:c.1278T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080476.5(PIGU):​c.1278T>G​(p.Asp426Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PIGU NM_080476.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.674

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2099162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGU	NM_080476.5	c.1278T>G	p.Asp426Glu	missense_variant	Exon 12 of 12	ENST00000217446.8	NP_536724.1
PIGU	XM_017027664.2	c.1134T>G	p.Asp378Glu	missense_variant	Exon 11 of 11		XP_016883153.1
PIGU	XM_011528542.2	c.630T>G	p.Asp210Glu	missense_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.1278T>G	p.Asp426Glu	missense_variant	Exon 12 of 12	1	NM_080476.5	ENSP00000217446.3
PIGU	ENST00000374820.6	c.1218T>G	p.Asp406Glu	missense_variant	Exon 11 of 11	1		ENSP00000363953.2
PIGU	ENST00000438215.1	c.*7T>G		downstream_gene_variant		3		ENSP00000395755.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459958 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726324

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.93	P;P
Vest4		0.38
MutPred		0.35		Loss of sheet (P = 0.0126);.;
MVP		0.18
MPC		0.58
ClinPred		0.85	D
GERP RS		0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14

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: chr20-33148700;