rs34227891

Positions:

• chr18-62143330-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_176787.5(PIGN):​c.939T>C​(p.Asn313Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,507,966 control chromosomes in the GnomAD database, including 48,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4536 hom., cov: 32)
  • Exomes 𝑓: 0.25 (44171 hom.)
• Consequence: PIGN NM_176787.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.238

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-62143330-A-G is Benign according to our data. Variant chr18-62143330-A-G is described in ClinVar as [Benign]. Clinvar id is 403305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.238 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGN	NM_176787.5	c.939T>C	p.Asn313Asn	synonymous_variant	11/31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.939T>C	p.Asn313Asn	synonymous_variant	11/31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.939T>C	p.Asn313Asn	synonymous_variant	10/30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.939T>C		non_coding_transcript_exon_variant	9/29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36106 AN: 151884 Hom.: 4533 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.192 AC: 38197 AN: 198452 Hom.: 4275 AF XY: 0.191 AC XY: 20208 AN XY: 105730

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.0681

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.247 AC: 334767 AN: 1355964 Hom.: 44171 Cov.: 23 AF XY: 0.245 AC XY: 165284 AN XY: 674710

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.0682

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.238 AC: 36132 AN: 152002 Hom.: 4536 Cov.: 32 AF XY: 0.233 AC XY: 17299 AN XY: 74300

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.0784

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.258

Alfa AF: 0.260 Hom.: 3744

Bravo AF: 0.233

Asia WGS AF: 0.132 AC: 458 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

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 -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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	-0.81
CADD	Benign	5.8
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs34227891; hg19: chr18-59810563; COSMIC: COSV62949022; COSMIC: COSV62949022;