rs9320000

Variant names:

• chr18-62147035-G-A
• rs9320000
• NM_176787.5:c.741C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-62147035-G-A
• chr18-62147035-G-C
• chr18-62147035-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_176787.5(PIGN):​c.741C>T​(p.His247His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,605,232 control chromosomes in the GnomAD database, including 308,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25655 hom., cov: 32)
  • Exomes 𝑓: 0.62 (282681 hom.)
• Consequence: PIGN NM_176787.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.661
• Publications: 20 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
• Fryns syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-62147035-G-A is Benign according to our data. Variant chr18-62147035-G-A is described in ClinVar as Benign. ClinVar VariationId is 403307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.661 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGN	NM_176787.5	c.741C>T	p.His247His	synonymous_variant	Exon 9 of 31	ENST00000640252.2	NP_789744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGN	ENST00000640252.2	c.741C>T	p.His247His	synonymous_variant	Exon 9 of 31	1	NM_176787.5	ENSP00000492233.1
PIGN	ENST00000400334.7	c.741C>T	p.His247His	synonymous_variant	Exon 8 of 30	1		ENSP00000383188.2
PIGN	ENST00000638424.1	n.741C>T		non_coding_transcript_exon_variant	Exon 7 of 29	5		ENSP00000491963.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87016 AN: 151862 Hom.: 25635 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.583

GnomAD2 exomes AF: 0.622 AC: 153387 AN: 246620 AF XY: 0.620

Gnomad AFR exome AF: 0.429

Gnomad AMR exome AF: 0.711

Gnomad ASJ exome AF: 0.641

Gnomad EAS exome AF: 0.680

Gnomad FIN exome AF: 0.603

Gnomad NFE exome AF: 0.612

Gnomad OTH exome AF: 0.626

GnomAD4 exome AF: 0.621 AC: 902803 AN: 1453252 Hom.: 282681 Cov.: 43 AF XY: 0.621 AC XY: 449139 AN XY: 723088

African (AFR) AF: 0.418 AC: 13951 AN: 33342

American (AMR) AF: 0.711 AC: 31628 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 16582 AN: 25978

East Asian (EAS) AF: 0.662 AC: 26120 AN: 39434

South Asian (SAS) AF: 0.627 AC: 53867 AN: 85926

European-Finnish (FIN) AF: 0.603 AC: 32094 AN: 53208

Middle Eastern (MID) AF: 0.647 AC: 3711 AN: 5734

European-Non Finnish (NFE) AF: 0.622 AC: 687901 AN: 1105084

Other (OTH) AF: 0.615 AC: 36949 AN: 60060

GnomAD4 genome AF: 0.573 AC: 87075 AN: 151980 Hom.: 25655 Cov.: 32 AF XY: 0.575 AC XY: 42733 AN XY: 74274

African (AFR) AF: 0.427 AC: 17698 AN: 41458

American (AMR) AF: 0.669 AC: 10229 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2233 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3541 AN: 5160

South Asian (SAS) AF: 0.637 AC: 3067 AN: 4818

European-Finnish (FIN) AF: 0.605 AC: 6380 AN: 10552

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41943 AN: 67934

Other (OTH) AF: 0.583 AC: 1227 AN: 2106

Alfa AF: 0.596 Hom.: 13891

Bravo AF: 0.575

Asia WGS AF: 0.632 AC: 2190 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:3

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:2

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Mar 11, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.31
DANN	Benign	0.41
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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: rs9320000; hg19: chr18-59814268; COSMIC: COSV62952158;