Variant chr16-583353-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000026218.9(PIGQ):c.2002T>C(p.Cys668Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,611,930 control chromosomes in the GnomAD database, including 166,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C668Y) has been classified as Benign.

Frequency

Genomes: 𝑓 0.46 ( 16177 hom., cov: 33)

Exomes 𝑓: 0.45 ( 150678 hom. )

Consequence

PIGQ
ENST00000026218.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.53

Variant links:

Genes affected

PIGQ (HGNC:14135): (phosphatidylinositol glycan anchor biosynthesis class Q) This gene is involved in the first step 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 gene encodes a N-acetylglucosaminyl transferase component that is part of the complex that catalyzes transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

PIGQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.912361E-6).

BP6

Variant 16-583353-T-C is Benign according to our data. Variant chr16-583353-T-C is described in ClinVar as [Benign]. Clinvar id is 1277846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5 linkuse as main transcript	c.*318T>C		3_prime_UTR_variant	11/11	ENST00000321878.10
PIGQ	NM_148920.4 linkuse as main transcript	c.2002T>C	p.Cys668Arg	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10 linkuse as main transcript	c.*318T>C		3_prime_UTR_variant	11/11	1	NM_004204.5	P1	Q9BRB3-2

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69176

AN:

151462

Hom.:

16148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.404

GnomAD3 exomes

AF:

0.488

AC:

121834

AN:

249866

Hom.:

30899

AF XY:

0.487

AC XY:

66023

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.617

Gnomad SAS exome

AF:

0.624

Gnomad FIN exome

AF:

0.507

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.448

AC:

654291

AN:

1460354

Hom.:

150678

Cov.:

AF XY:

0.452

AC XY:

328380

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.549

Gnomad4 ASJ exome

AF:

0.381

Gnomad4 EAS exome

AF:

0.667

Gnomad4 SAS exome

AF:

0.621

Gnomad4 FIN exome

AF:

0.513

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.457

AC:

69256

AN:

151576

Hom.:

16177

Cov.:

AF XY:

0.465

AC XY:

34447

AN XY:

74048

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.379

Gnomad4 EAS

AF:

0.637

Gnomad4 SAS

AF:

0.628

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.417

Gnomad4 OTH

AF:

0.411

Alfa

AF:

0.427

Hom.:

6794

Bravo

AF:

0.451

TwinsUK

AF:

0.399

AC:

1479

ALSPAC

AF:

0.414

AC:

1594

ESP6500AA

AF:

0.447

AC:

1968

ESP6500EA

AF:

0.390

AC:

3354

ExAC

AF:

0.489

AC:

59291

Asia WGS

AF:

0.658

AC:

2291

AN:

3478

EpiCase

AF:

0.395

EpiControl

AF:

0.388

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 72% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 67. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.6

DANN

Benign

0.49

DEOGEN2

Benign

0.027

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000069

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

0.0

REVEL

Benign

0.015

Sift

Pathogenic

0.0

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.015

MPC

0.24

ClinPred

0.0069

GERP RS

1.3

Varity_R

0.48

gMVP

0.024

Splicing

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