18-62045677-G-GAA

Variant names:

• chr18-62045677-G-GAA
• rs3833870
• NM_176787.5:c.*177_*178dupTT

Variant summary

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

The NM_176787.5(PIGN):​c.*177_*178dupTT 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: 𝑓 0.000040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: PIGN NM_176787.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• Publications: 3 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• 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.*177_*178dupTT		3_prime_UTR	Exon 31 of 31	NP_789744.1	O95427
	PIGN	NM_001438896.1		c.*177_*178dupTT		3_prime_UTR	Exon 32 of 32	NP_001425825.1
	PIGN	NM_012327.6		c.*177_*178dupTT		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.*177_*178dupTT		3_prime_UTR	Exon 31 of 31	ENSP00000492233.1	O95427
	PIGN	ENST00000400334.7	TSL:1	c.*177_*178dupTT		3_prime_UTR	Exon 30 of 30	ENSP00000383188.2	O95427
	PIGN	ENST00000638424.1	TSL:5	n.*941_*942dupTT		non_coding_transcript_exon	Exon 29 of 29	ENSP00000491963.1	A0A1W2PQZ1

Frequencies

GnomAD3 genomes AF: 0.0000397 AC: 6 AN: 151270 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0121 AC: 3663 AN: 301794 Hom.: 0 Cov.: 6 AF XY: 0.0123 AC XY: 1915 AN XY: 155584

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

African (AFR) AF: 0.00329 AC: 32 AN: 9738

American (AMR) AF: 0.0173 AC: 186 AN: 10762

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 114 AN: 8980

East Asian (EAS) AF: 0.0162 AC: 339 AN: 20968

South Asian (SAS) AF: 0.0132 AC: 236 AN: 17908

European-Finnish (FIN) AF: 0.0127 AC: 246 AN: 19374

Middle Eastern (MID) AF: 0.00992 AC: 15 AN: 1512

European-Non Finnish (NFE) AF: 0.0118 AC: 2298 AN: 195112

Other (OTH) AF: 0.0113 AC: 197 AN: 17440

⚠️ 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 AF: 0.0000396 AC: 6 AN: 151386 Hom.: 0 Cov.: 0 AF XY: 0.0000271 AC XY: 2 AN XY: 73924

African (AFR) AF: 0.0000243 AC: 1 AN: 41214

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.00 Hom.: 705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3833870; hg19: chr18-59712910;