18-62045731-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_176787.5(PIGN):c.*125A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00787 in 874,274 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (30 hom.)
• Consequence: PIGN NM_176787.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.689

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-62045731-T-C is Benign according to our data. Variant chr18-62045731-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1203448.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00624 (950/152296) while in subpopulation NFE AF= 0.00928 (631/68020). AF 95% confidence interval is 0.00868. There are 5 homozygotes in gnomad4. There are 450 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGN	NM_176787.5	c.*125A>G		3_prime_UTR_variant	31/31	ENST00000640252.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGN	ENST00000640252.2	c.*125A>G		3_prime_UTR_variant	31/31	1	NM_176787.5	P1

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 950 AN: 152178 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00928

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.00821 AC: 5931 AN: 721978 Hom.: 30 Cov.: 10 AF XY: 0.00824 AC XY: 2980 AN XY: 361440

Gnomad4 AFR exome AF: 0.000826

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.000283

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00416

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.00921

Gnomad4 OTH exome AF: 0.00814

GnomAD4 genome AF: 0.00624 AC: 950 AN: 152296 Hom.: 5 Cov.: 32 AF XY: 0.00604 AC XY: 450 AN XY: 74468

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.00928

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00770 Hom.: 2

Bravo AF: 0.00560

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.13
Dann	Benign	0.71

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: rs112427873; hg19: chr18-59712964;