1-172442356-A-G

Position:

• chr1-172442356-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_153747.2(PIGC):​c.267T>C​(p.Gly89Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,612,940 control chromosomes in the GnomAD database, including 582,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (57064 hom., cov: 31)
  • Exomes 𝑓: 0.85 (525036 hom.)
• Consequence: PIGC NM_153747.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.136

Genes affected

PIGC (HGNC:8960): (phosphatidylinositol glycan anchor biosynthesis class C) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI) lipid anchor biosynthesis. The GPI lipid anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. The encoded protein is one subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. Two alternatively spliced transcripts that encode the same protein have been found for this gene. A pseudogene on chromosome 11 has also been characterized. [provided by RefSeq, Jul 2008]

C1orf105 (HGNC:29591): (chromosome 1 open reading frame 105)

PIGC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-172442356-A-G is Benign according to our data. Variant chr1-172442356-A-G is described in ClinVar as [Benign]. Clinvar id is 595495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.136 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGC	NM_153747.2	c.267T>C	p.Gly89Gly	synonymous_variant	2/2	ENST00000344529.5	NP_714969.1
C1orf105	NM_139240.4	c.22-2717A>G		intron_variant		ENST00000367727.9	NP_640333.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGC	ENST00000344529.5	c.267T>C	p.Gly89Gly	synonymous_variant	2/2	1	NM_153747.2	ENSP00000356701.3
C1orf105	ENST00000367727.9	c.22-2717A>G		intron_variant		1	NM_139240.4	ENSP00000356700.4

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131449 AN: 152020 Hom.: 57026 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.899

GnomAD3 exomes AF: 0.874 AC: 219695 AN: 251388 Hom.: 96563 AF XY: 0.875 AC XY: 118945 AN XY: 135866

Gnomad AFR exome AF: 0.892

Gnomad AMR exome AF: 0.904

Gnomad ASJ exome AF: 0.924

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.938

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.839

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.846 AC: 1236322 AN: 1460802 Hom.: 525036 Cov.: 63 AF XY: 0.850 AC XY: 617413 AN XY: 726730

Gnomad4 AFR exome AF: 0.896

Gnomad4 AMR exome AF: 0.905

Gnomad4 ASJ exome AF: 0.924

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.935

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.830

Gnomad4 OTH exome AF: 0.866

GnomAD4 genome AF: 0.865 AC: 131545 AN: 152138 Hom.: 57064 Cov.: 31 AF XY: 0.865 AC XY: 64332 AN XY: 74364

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.900

Alfa AF: 0.850 Hom.: 28314

Bravo AF: 0.877

Asia WGS AF: 0.964 AC: 3354 AN: 3478

EpiCase AF: 0.854

EpiControl AF: 0.859

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 04, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 21, 2017

- -

PIGC-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Glycosylphosphatidylinositol biosynthesis defect 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.8
DANN	Benign	0.80

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: rs2230471; hg19: chr1-172411496; COSMIC: COSV51129928; COSMIC: COSV51129928;