18-62087057-C-T

Variant names:

• chr18-62087057-C-T
• rs663354
• NM_176787.5:c.2370+1699G>A

Variant summary

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

The NM_176787.5(PIGN):​c.2370+1699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,756 control chromosomes in the GnomAD database, including 4,683 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 0.24 (4683 hom., cov: 31)
• Consequence: PIGN NM_176787.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 5 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5	c.2370+1699G>A		intron_variant	Intron 25 of 30	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.2370+1699G>A		intron_variant	Intron 25 of 30	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.2370+1699G>A		intron_variant	Intron 24 of 29	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.*338+1334G>A		intron_variant	Intron 23 of 28	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37106 AN: 151638 Hom.: 4676 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.245 AC: 37124 AN: 151756 Hom.: 4683 Cov.: 31 AF XY: 0.242 AC XY: 17977 AN XY: 74154

African (AFR) AF: 0.237 AC: 9776 AN: 41324

American (AMR) AF: 0.213 AC: 3249 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3466

East Asian (EAS) AF: 0.0915 AC: 473 AN: 5170

South Asian (SAS) AF: 0.166 AC: 799 AN: 4810

European-Finnish (FIN) AF: 0.259 AC: 2724 AN: 10498

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18455 AN: 67928

Other (OTH) AF: 0.248 AC: 521 AN: 2104

Alfa AF: 0.238 Hom.: 2319

Bravo AF: 0.240

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.77
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs663354; hg19: chr18-59754290;