NM_002641.4:c.*7G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002641.4(PIGA):c.*7G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000744 in 1,188,589 control chromosomes in the GnomAD database, including 12 homozygotes. There are 222 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., 110 hem., cov: 23)

Exomes 𝑓: 0.00044 ( 9 hom. 112 hem. )

Consequence

PIGA
NM_002641.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.162

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
multiple congenital anomalies-hypotonia-seizures syndrome 2
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ferro-cerebro-cutaneous syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
paroxysmal nocturnal hemoglobinuria
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

PIGA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-15321499-C-A is Benign according to our data. Variant chrX-15321499-C-A is described in ClinVar as Benign. ClinVar VariationId is 383130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 412 Unknown,XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIGA	NM_002641.4	MANE Select	c.*7G>T	3_prime_UTR	Exon 6 of 6	NP_002632.1	P37287-1
PIGA	NM_001440789.1		c.*7G>T	3_prime_UTR	Exon 7 of 7	NP_001427718.1
PIGA	NM_001440790.1		c.*7G>T	3_prime_UTR	Exon 6 of 6	NP_001427719.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIGA	ENST00000333590.6	TSL:1 MANE Select	c.*7G>T	3_prime_UTR	Exon 6 of 6	ENSP00000369820.3	P37287-1
PIGA	ENST00000542278.6	TSL:5	c.*7G>T	3_prime_UTR	Exon 6 of 6	ENSP00000442653.2	P37287-1
PIGA	ENST00000482148.6	TSL:5	c.*7G>T	3_prime_UTR	Exon 5 of 5	ENSP00000489528.1	P37287-2

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

413

AN:

112296

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

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:

0.0000751

Gnomad OTH

AF:

0.00396

GnomAD2 exomes

AF:

0.00110

AC:

198

AN:

180642

AF XY:

0.000610

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.000451

GnomAD4 exome

AF:

0.000439

AC:

472

AN:

1076240

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

112

AN XY:

343892

show subpopulations

African (AFR)

AF:

0.0153

AC:

395

AN:

25860

American (AMR)

AF:

0.000430

AC:

AN:

34869

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19116

East Asian (EAS)

AF:

0.00

AC:

AN:

30064

South Asian (SAS)

AF:

0.0000375

AC:

AN:

53394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40479

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

4058

European-Non Finnish (NFE)

AF:

0.0000219

AC:

AN:

823091

Other (OTH)

AF:

0.000817

AC:

AN:

45309

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00367

AC:

412

AN:

112349

Hom.:

Cov.:

AF XY:

0.00319

AC XY:

110

AN XY:

34517

show subpopulations

African (AFR)

AF:

0.0129

AC:

400

AN:

30929

American (AMR)

AF:

0.000189

AC:

AN:

10584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3616

South Asian (SAS)

AF:

0.00

AC:

AN:

2762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000751

AC:

AN:

53260

Other (OTH)

AF:

0.00391

AC:

AN:

1535

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000556

Hom.:

Bravo

AF:

0.00459

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

PIGA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.9

(source)

DANN

Benign

0.62

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over