rs10503060

Variant names:

• chr18-61933093-G-A
• rs10503060
• ENST00000639600.1:c.*2-27601C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000639600.1(PIGN):​c.*2-27601C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,058 control chromosomes in the GnomAD database, including 3,431 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3431 hom., cov: 32)
• Consequence: PIGN ENST00000639600.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 0 publications found

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]

PIGN Gene-Disease associations (from GenCC):

• multiple congenital anomalies-hypotonia-seizures syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
• Fryns syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303698 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000639600.1	c.*2-27601C>T		intron_variant	Intron 24 of 24	5		ENSP00000492474.1
ENSG00000303698	ENST00000796617.1	n.200-108G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29838 AN: 151940 Hom.: 3427 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29876 AN: 152058 Hom.: 3431 Cov.: 32 AF XY: 0.196 AC XY: 14531 AN XY: 74294

African (AFR) AF: 0.109 AC: 4532 AN: 41498

American (AMR) AF: 0.155 AC: 2369 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3468

East Asian (EAS) AF: 0.0634 AC: 328 AN: 5172

South Asian (SAS) AF: 0.115 AC: 554 AN: 4828

European-Finnish (FIN) AF: 0.306 AC: 3228 AN: 10532

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17503 AN: 67968

Other (OTH) AF: 0.206 AC: 436 AN: 2114

Alfa AF: 0.222 Hom.: 511

Bravo AF: 0.183

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.89
DANN	Benign	0.20
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10503060; hg19: chr18-59600326;