18-62045677-GA-GAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_176787.5(PIGN):​c.*178dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21959 hom., cov: 0)
  • Exomes 𝑓: 0.52 (36800 hom.)
• Consequence: PIGN NM_176787.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Fryns syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 18-62045677-G-GA is Benign according to our data. Variant chr18-62045677-G-GA is described in ClinVar as Benign. ClinVar VariationId is 1224902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGN	NM_176787.5	MANE Select	c.*178dupT		3_prime_UTR	Exon 31 of 31	NP_789744.1	O95427
	PIGN	NM_001438896.1		c.*178dupT		3_prime_UTR	Exon 32 of 32	NP_001425825.1
	PIGN	NM_012327.6		c.*178dupT		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.*178dupT		3_prime_UTR	Exon 31 of 31	ENSP00000492233.1	O95427
	PIGN	ENST00000400334.7	TSL:1	c.*178dupT		3_prime_UTR	Exon 30 of 30	ENSP00000383188.2	O95427
	PIGN	ENST00000638424.1	TSL:5	n.*942dupT		non_coding_transcript_exon	Exon 29 of 29	ENSP00000491963.1	A0A1W2PQZ1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 77896 AN: 151198 Hom.: 21952 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.517 AC: 158315 AN: 306490 Hom.: 36800 Cov.: 6 AF XY: 0.517 AC XY: 81643 AN XY: 157882

African (AFR) AF: 0.238 AC: 2313 AN: 9704

American (AMR) AF: 0.578 AC: 6334 AN: 10966

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 4962 AN: 9134

East Asian (EAS) AF: 0.592 AC: 12735 AN: 21510

South Asian (SAS) AF: 0.517 AC: 9417 AN: 18226

European-Finnish (FIN) AF: 0.567 AC: 11188 AN: 19724

Middle Eastern (MID) AF: 0.494 AC: 758 AN: 1534

European-Non Finnish (NFE) AF: 0.514 AC: 101764 AN: 198026

Other (OTH) AF: 0.501 AC: 8844 AN: 17666

GnomAD4 genome AF: 0.515 AC: 77930 AN: 151314 Hom.: 21959 Cov.: 0 AF XY: 0.523 AC XY: 38665 AN XY: 73894

African (AFR) AF: 0.268 AC: 11054 AN: 41178

American (AMR) AF: 0.625 AC: 9516 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2131 AN: 3460

East Asian (EAS) AF: 0.707 AC: 3642 AN: 5152

South Asian (SAS) AF: 0.613 AC: 2929 AN: 4778

European-Finnish (FIN) AF: 0.651 AC: 6763 AN: 10396

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40079 AN: 67820

Other (OTH) AF: 0.520 AC: 1092 AN: 2098

Alfa AF: 0.330 Hom.: 705

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV62948933; COSMIC: COSV62948933;