rs61751989

Positions:

• chr18-62146032-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176787.5(PIGN):​c.806-7T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,302,290 control chromosomes in the GnomAD database, including 36,857 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3711 hom., cov: 32)
  • Exomes 𝑓: 0.23 (33146 hom.)
• Consequence: PIGN NM_176787.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.704

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 18-62146032-A-T is Benign according to our data. Variant chr18-62146032-A-T is described in ClinVar as [Benign]. Clinvar id is 403306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGN	NM_176787.5	c.806-7T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.806-7T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_176787.5	ENSP00000492233	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32267 AN: 151946 Hom.: 3710 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.221

GnomAD3 exomes AF: 0.196 AC: 40291 AN: 205274 Hom.: 4453 AF XY: 0.197 AC XY: 22076 AN XY: 111960

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.00284

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.234 AC: 268913 AN: 1150226 Hom.: 33146 Cov.: 15 AF XY: 0.231 AC XY: 134461 AN XY: 582682

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.00127

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.212 AC: 32289 AN: 152064 Hom.: 3711 Cov.: 32 AF XY: 0.207 AC XY: 15398 AN XY: 74310

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.223

Alfa AF: 0.238 Hom.: 1469

Bravo AF: 0.208

Asia WGS AF: 0.0870 AC: 306 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs61751989; hg19: chr18-59813265;