X-15321541-C-G

Variant names:

• chrX-15321541-C-G
• NM_002641.4:c.1420G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002641.4(PIGA):​c.1420G>C​(p.Gly474Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,589 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: PIGA NM_002641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022291094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGA	NM_002641.4	c.1420G>C	p.Gly474Arg	missense_variant	Exon 6 of 6	ENST00000333590.6	NP_002632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGA	ENST00000333590.6	c.1420G>C	p.Gly474Arg	missense_variant	Exon 6 of 6	1	NM_002641.4	ENSP00000369820.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092589 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 358241

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.19
DEOGEN2	Benign	0.10	T;T;T;.;.
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.61	.;T;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.022	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N;.;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.14	N;.;.;.;.
REVEL	Benign	0.0090
Sift	Benign	0.65	T;.;.;.;.
Sift4G	Benign	0.70	T;T;.;T;T
Polyphen		0.0	B;B;.;.;B
Vest4		0.060
MutPred		0.10		Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);.;.;.;
MVP		0.12
MPC		0.67
ClinPred		0.012	T
GERP RS		-8.2
Varity_R		0.045
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-15339663;