Variant X-15321466-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002641.4(PIGA):c.*40G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 1,130,223 control chromosomes in the GnomAD database, including 178 homozygotes. There are 1,846 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 84 hom., 742 hem., cov: 23)

Exomes 𝑓: 0.0042 ( 94 hom. 1104 hem. )

Consequence

PIGA
NM_002641.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.164

Variant links:

Genes affected

PIGA (HGNC:8957): (phosphatidylinositol glycan anchor biosynthesis class A) This gene encodes a protein required for synthesis of N-acetylglucosaminyl phosphatidylinositol (GlcNAc-PI), the first intermediate in the biosynthetic pathway of GPI anchor. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. Paroxysmal nocturnal hemoglobinuria, an acquired hematologic disorder, has been shown to result from mutations in this gene. Alternate splice variants have been characterized. A related pseudogene is located on chromosome 12. [provided by RefSeq, Jun 2010]

PIGA links:

PIGA (HGNC:):

PIGA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-15321466-C-T is Benign according to our data. Variant chrX-15321466-C-T is described in ClinVar as [Benign]. Clinvar id is 1228500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGA	NM_002641.4 linkuse as main transcript	c.*40G>A		3_prime_UTR_variant	6/6	ENST00000333590.6	NP_002632.1	P37287-1A0A2K4ZA02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGA	ENST00000333590 linkuse as main transcript	c.*40G>A		3_prime_UTR_variant	6/6	1	NM_002641.4	ENSP00000369820.3		P37287-1

Frequencies

GnomAD3 genomes

AF:

0.0256

AC:

2872

AN:

112190

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

734

AN XY:

34376

show subpopulations

Gnomad AFR

AF:

0.0828

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00493

Gnomad EAS

AF:

0.000276

Gnomad SAS

AF:

0.00108

Gnomad FIN

AF:

0.000495

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.0265

GnomAD3 exomes

AF:

0.00857

AC:

1412

AN:

164743

Hom.:

AF XY:

0.00654

AC XY:

359

AN XY:

54859

show subpopulations

Gnomad AFR exome

AF:

0.0891

Gnomad AMR exome

AF:

0.00556

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000867

Gnomad FIN exome

AF:

0.000534

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00424

AC:

4314

AN:

1017979

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

1104

AN XY:

303509

show subpopulations

Gnomad4 AFR exome

AF:

0.0909

Gnomad4 AMR exome

AF:

0.00571

Gnomad4 ASJ exome

AF:

0.00418

Gnomad4 EAS exome

AF:

0.0000336

Gnomad4 SAS exome

AF:

0.000618

Gnomad4 FIN exome

AF:

0.000476

Gnomad4 NFE exome

AF:

0.00184

Gnomad4 OTH exome

AF:

0.00798

GnomAD4 genome

AF:

0.0257

AC:

2886

AN:

112244

Hom.:

Cov.:

AF XY:

0.0215

AC XY:

742

AN XY:

34440

show subpopulations

Gnomad4 AFR

AF:

0.0831

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.00493

Gnomad4 EAS

AF:

0.000277

Gnomad4 SAS

AF:

0.00108

Gnomad4 FIN

AF:

0.000495

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.0262

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.0293

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.27

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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