rs1063412

Positions:

chr1-172441827-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_153747.2(PIGC):c.796C>T(p.Pro266Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.547 in 1,613,024 control chromosomes in the GnomAD database, including 249,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.45 ( 18407 hom., cov: 33)

Exomes 𝑓: 0.56 ( 231151 hom. )

Consequence

PIGC
NM_153747.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.19

Variant links:

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]

PIGC links:

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

C1orf105 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a chain Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (size 296) in uniprot entity PIGC_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_153747.2

BP4

Computational evidence support a benign effect (MetaRNN=1.0123705E-4).

BP6

Variant 1-172441827-G-A is Benign according to our data. Variant chr1-172441827-G-A is described in ClinVar as [Benign]. Clinvar id is 1327021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGC	NM_153747.2 linkuse as main transcript	c.796C>T	p.Pro266Ser	missense_variant	2/2	ENST00000344529.5
C1orf105	NM_139240.4 linkuse as main transcript	c.22-3246G>A		intron_variant		ENST00000367727.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIGC	ENST00000344529.5 linkuse as main transcript	c.796C>T	p.Pro266Ser	missense_variant	2/2	1	NM_153747.2	P1
C1orf105	ENST00000367727.9 linkuse as main transcript	c.22-3246G>A		intron_variant		1	NM_139240.4	P1
PIGC	ENST00000484368.1 linkuse as main transcript	n.96+2161C>T		intron_variant, non_coding_transcript_variant		1
PIGC	ENST00000367728.1 linkuse as main transcript	c.796C>T	p.Pro266Ser	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68708

AN:

152014

Hom.:

18418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.529

Gnomad EAS

AF:

0.648

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.497

GnomAD3 exomes

AF:

0.557

AC:

139685

AN:

250962

Hom.:

40646

AF XY:

0.564

AC XY:

76428

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.544

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.577

GnomAD4 exome

AF:

0.557

AC:

814280

AN:

1460892

Hom.:

231151

Cov.:

AF XY:

0.560

AC XY:

406872

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.611

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.651

Gnomad4 SAS exome

AF:

0.574

Gnomad4 FIN exome

AF:

0.590

Gnomad4 NFE exome

AF:

0.563

Gnomad4 OTH exome

AF:

0.540

GnomAD4 genome

AF:

0.452

AC:

68700

AN:

152132

Hom.:

18407

Cov.:

AF XY:

0.457

AC XY:

34013

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.553

Gnomad4 ASJ

AF:

0.529

Gnomad4 EAS

AF:

0.648

Gnomad4 SAS

AF:

0.575

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.566

Gnomad4 OTH

AF:

0.491

Alfa

AF:

0.551

Hom.:

51111

Bravo

AF:

0.438

TwinsUK

AF:

0.550

AC:

2040

ALSPAC

AF:

0.563

AC:

2168

ESP6500AA

AF:

0.151

AC:

665

ESP6500EA

AF:

0.557

AC:

4793

ExAC

AF:

0.548

AC:

66498

Asia WGS

AF:

0.527

AC:

1836

AN:

3478

EpiCase

AF:

0.573

EpiControl

AF:

0.574

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

.;T

MetaRNN

Benign

0.00010

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

2.8e-30

P;P;P;P

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.1

D;D

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.90

MPC

0.57

ClinPred

0.042

GERP RS

4.2

Varity_R

0.72

gMVP

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over