X-15321217-TATA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002641.4(PIGA):c.*286_*288del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 201,960 control chromosomes in the GnomAD database, including 8 homozygotes. There are 193 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (8 hom., 181 hem., cov: 23)
  • Exomes 𝑓: 0.00094 (0 hom. 12 hem.)
• Consequence: PIGA NM_002641.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-15321217-TATA-T is Benign according to our data. Variant chrX-15321217-TATA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1185707.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00568 (635/111878) while in subpopulation AFR AF= 0.0197 (606/30794). AF 95% confidence interval is 0.0184. There are 8 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGA	NM_002641.4	c.*286_*288del		3_prime_UTR_variant	6/6	ENST00000333590.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGA	ENST00000333590.6	c.*286_*288del		3_prime_UTR_variant	6/6	1	NM_002641.4	P1

Frequencies

GnomAD3 genomes AF: 0.00566 AC: 633 AN: 111823 Hom.: 8 Cov.: 23 AF XY: 0.00532 AC XY: 181 AN XY: 33999

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00218

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: 0.0000564

Gnomad OTH AF: 0.00198

GnomAD4 exome AF: 0.000944 AC: 85 AN: 90082 Hom.: 0 AF XY: 0.000680 AC XY: 12 AN XY: 17644

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.00160

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: 0.0000173

Gnomad4 OTH exome AF: 0.00168

GnomAD4 genome AF: 0.00568 AC: 635 AN: 111878 Hom.: 8 Cov.: 23 AF XY: 0.00531 AC XY: 181 AN XY: 34064

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.00218

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000564

Gnomad4 OTH AF: 0.00196

Alfa AF: 0.00541 Hom.: 16

Bravo AF: 0.00667

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs753691551; hg19: chrX-15339339;