18-62045677-GA-G

Variant names:

• chr18-62045677-GA-G
• rs3833870
• NM_176787.5:c.*178delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_176787.5(PIGN):​c.*178delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: PIGN NM_176787.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• 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: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Fryns syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGN	NM_176787.5	MANE Select	c.*178delT		3_prime_UTR	Exon 31 of 31	NP_789744.1	O95427
	PIGN	NM_001438896.1		c.*178delT		3_prime_UTR	Exon 32 of 32	NP_001425825.1
	PIGN	NM_012327.6		c.*178delT		3_prime_UTR	Exon 30 of 30	NP_036459.1	O95427

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGN	ENST00000640252.2	TSL:1 MANE Select	c.*178delT		3_prime_UTR	Exon 31 of 31	ENSP00000492233.1	O95427
	PIGN	ENST00000400334.7	TSL:1	c.*178delT		3_prime_UTR	Exon 30 of 30	ENSP00000383188.2	O95427
	PIGN	ENST00000638424.1	TSL:5	n.*942delT		non_coding_transcript_exon	Exon 29 of 29	ENSP00000491963.1	A0A1W2PQZ1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000519 AC: 16 AN: 308056 Hom.: 0 Cov.: 6 AF XY: 0.0000630 AC XY: 10 AN XY: 158740

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000102 AC: 1 AN: 9770

American (AMR) AF: 0.00 AC: 0 AN: 11022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9184

East Asian (EAS) AF: 0.00 AC: 0 AN: 21588

South Asian (SAS) AF: 0.0000545 AC: 1 AN: 18348

European-Finnish (FIN) AF: 0.0000505 AC: 1 AN: 19812

Middle Eastern (MID) AF: 0.000649 AC: 1 AN: 1542

European-Non Finnish (NFE) AF: 0.0000603 AC: 12 AN: 199018

Other (OTH) AF: 0.00 AC: 0 AN: 17772

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

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: rs3833870; hg19: chr18-59712910;