rs677295

Variant names:

• chr18-62094423-C-T
• rs677295
• NM_176787.5:c.2180+1425G>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.2180+1425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,982 control chromosomes in the GnomAD database, including 4,239 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 0.23 (4239 hom., cov: 32)
• Consequence: PIGN NM_176787.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176787.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGN	NM_176787.5	MANE Select	c.2180+1425G>A		intron	N/A	NP_789744.1
	PIGN	NM_001438896.1		c.2180+1425G>A		intron	N/A	NP_001425825.1
	PIGN	NM_012327.6		c.2180+1425G>A		intron	N/A	NP_036459.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGN	ENST00000640252.2	TSL:1 MANE Select	c.2180+1425G>A		intron	N/A	ENSP00000492233.1
	PIGN	ENST00000400334.7	TSL:1	c.2180+1425G>A		intron	N/A	ENSP00000383188.2
	PIGN	ENST00000638424.1	TSL:5	n.2180+1425G>A		intron	N/A	ENSP00000491963.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35184 AN: 151864 Hom.: 4234 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.232 AC: 35197 AN: 151982 Hom.: 4239 Cov.: 32 AF XY: 0.230 AC XY: 17073 AN XY: 74278

African (AFR) AF: 0.198 AC: 8230 AN: 41464

American (AMR) AF: 0.207 AC: 3155 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3466

East Asian (EAS) AF: 0.0915 AC: 474 AN: 5182

South Asian (SAS) AF: 0.164 AC: 789 AN: 4818

European-Finnish (FIN) AF: 0.258 AC: 2721 AN: 10540

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18233 AN: 67926

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.252 Hom.: 2221

Bravo AF: 0.225

Asia WGS AF: 0.148 AC: 513 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.78
PhyloP100		0.12
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: rs677295; hg19: chr18-59761656;