Variant 20-34575198-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080476.5(PIGU):c.1100T>C(p.Leu367Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PIGU
NM_080476.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGU	NM_080476.5 link	c.1100T>C	p.Leu367Pro	missense_variant	11/12	ENST00000217446.8	NP_536724.1	Q9H490-1
PIGU	XM_017027664.2 link	c.956T>C	p.Leu319Pro	missense_variant	10/11		XP_016883153.1
PIGU	XM_011528542.2 link	c.452T>C	p.Leu151Pro	missense_variant	5/6		XP_011526844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIGU	ENST00000217446.8 link	c.1100T>C	p.Leu367Pro	missense_variant	11/12	1	NM_080476.5	ENSP00000217446.3	Q9H490-1
PIGU	ENST00000374820.6 link	c.1040T>C	p.Leu347Pro	missense_variant	10/11	1		ENSP00000363953.2	Q9H490-2
PIGU	ENST00000438215.1 link	c.338T>C	p.Leu113Pro	missense_variant	5/6	3		ENSP00000395755.1	Q5JWU1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251442

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.1100T>C (p.L367P) alteration is located in exon 11 (coding exon 11) of the PIGU gene. This alteration results from a T to C substitution at nucleotide position 1100, causing the leucine (L) at amino acid position 367 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

T;.;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.4

M;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.051

T;T;.

Polyphen

0.97

D;D;.

Vest4

0.82

MutPred

0.81

Loss of stability (P = 0.0404);.;.;

MVP

0.39

MPC

0.86

ClinPred

0.91

GERP RS

5.4

Varity_R

0.79

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over