X-15321420-CA-C

Variant summary

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

The NM_002641.4(PIGA):c.*85del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 867,778 control chromosomes in the GnomAD database, including 16 homozygotes. There are 287 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (9 hom., 174 hem., cov: 22)
  • Exomes 𝑓: 0.00065 (7 hom. 113 hem.)
• Consequence: PIGA NM_002641.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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-15321420-CA-C is Benign according to our data. Variant chrX-15321420-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1212595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0056 (628/112085) while in subpopulation AFR AF= 0.0194 (599/30866). AF 95% confidence interval is 0.0181. There are 9 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGA	NM_002641.4	c.*85del		3_prime_UTR_variant	6/6	ENST00000333590.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGA	ENST00000333590.6	c.*85del		3_prime_UTR_variant	6/6	1	NM_002641.4	P1

Frequencies

GnomAD3 genomes AF: 0.00559 AC: 626 AN: 112033 Hom.: 9 Cov.: 22 AF XY: 0.00508 AC XY: 174 AN XY: 34231

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00228

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: 0.0000376

Gnomad OTH AF: 0.00199

GnomAD4 exome AF: 0.000650 AC: 491 AN: 755693 Hom.: 7 Cov.: 12 AF XY: 0.000557 AC XY: 113 AN XY: 202853

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.000841

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000108

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000356

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.00560 AC: 628 AN: 112085 Hom.: 9 Cov.: 22 AF XY: 0.00507 AC XY: 174 AN XY: 34293

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.00227

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000376

Gnomad4 OTH AF: 0.00197

Alfa AF: 0.00548 Hom.: 16

Bravo AF: 0.00668

Asia WGS AF: 0.000398 AC: 1 AN: 2522

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

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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: rs202201866; hg19: chrX-15339542;