Variant X-15335513-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 8P and 12B. PVS1BP6_Very_StrongBS2

The NM_020473.3(PIGA):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 976,358 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 105 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., 22 hem., cov: 25)

Exomes 𝑓: 0.00029 ( 0 hom. 83 hem. )

Consequence

PIGA
NM_020473.3 start_lost

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.192

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 Likely_benign. Variant got -4 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BP6

Variant X-15335513-T-C is Benign according to our data. Variant chrX-15335513-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 376854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-15335513-T-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGA	NM_002641.4 linkuse as main transcript	c.-75A>G		5_prime_UTR_variant	1/6	ENST00000333590.6	NP_002632.1	P37287-1A0A2K4ZA02
PIGA	NM_020473.3 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/5		NP_065206.3	P37287-3
PIGA	NR_033835.1 linkuse as main transcript	n.42A>G		non_coding_transcript_exon_variant	1/6
PIGA	NR_033836.1 linkuse as main transcript	n.42A>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGA	ENST00000333590.6 linkuse as main transcript	c.-75A>G		5_prime_UTR_variant	1/6	1	NM_002641.4	ENSP00000369820.3		P37287-1

Frequencies

GnomAD3 genomes

AF:

0.000547

AC:

AN:

113320

Hom.:

Cov.:

AF XY:

0.000620

AC XY:

AN XY:

35462

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000289

AC:

AN:

6932

Hom.:

AF XY:

0.00

AC XY:

AN XY:

450

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000600

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000286

AC:

247

AN:

863038

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

AN XY:

265796

show subpopulations

Gnomad4 AFR exome

AF:

0.00171

Gnomad4 AMR exome

AF:

0.000120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.000424

GnomAD4 genome

AF:

0.000547

AC:

AN:

113320

Hom.:

Cov.:

AF XY:

0.000620

AC XY:

AN XY:

35462

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.000367

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000627

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 07, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Oct 27, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

Sift4G

Pathogenic

0.0

Vest4

0.38

MutPred

0.54

Loss of disorder (P = 0.1638);

ClinPred

0.15

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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