rs138671843

chr18-62074825-GA-Gchr18-62074825-GA-GAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_176787.5(PIGN):c.2577-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,572,492 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: PIGN NM_176787.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0730

Genes affected

PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-62074825-GA-G is Benign according to our data. Variant chr18-62074825-GA-G is described in ClinVar as [Benign]. Clinvar id is 1610886.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGN	NM_176787.5	c.2577-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000640252.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGN	ENST00000640252.2	c.2577-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_176787.5	P1

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000116 AC: 165 AN: 1422300 Hom.: 1 Cov.: 26 AF XY: 0.000109 AC XY: 77 AN XY: 707718

Gnomad4 AFR exome AF: 0.0000617

Gnomad4 AMR exome AF: 0.0000930

Gnomad4 ASJ exome AF: 0.000118

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.000133

Gnomad4 FIN exome AF: 0.0000381

Gnomad4 NFE exome AF: 0.0000877

Gnomad4 OTH exome AF: 0.0000681

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150192 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73236

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs138671843; hg19: chr18-59742058;