rs2071979

Positions:

chr16-574114-A-G

Variant summary

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

The NM_004204.5(PIGQ):c.40A>G(p.Thr14Ala) variant causes a missense change. The variant allele was found at a frequency of 0.448 in 1,609,226 control chromosomes in the GnomAD database, including 166,056 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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.

Frequency

Genomes: 𝑓 0.46 ( 16570 hom., cov: 34)

Exomes 𝑓: 0.45 ( 149486 hom. )

Consequence

PIGQ
NM_004204.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.63

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=1.4899833E-5).

BP6

Variant 16-574114-A-G is Benign according to our data. Variant chr16-574114-A-G is described in ClinVar as [Benign]. Clinvar id is 1164853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGQ	NM_004204.5 linkuse as main transcript	c.40A>G	p.Thr14Ala	missense_variant	2/11	ENST00000321878.10	NP_004195.2
PIGQ	NM_148920.4 linkuse as main transcript	c.40A>G	p.Thr14Ala	missense_variant	2/10		NP_683721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10 linkuse as main transcript	c.40A>G	p.Thr14Ala	missense_variant	2/11	1	NM_004204.5	ENSP00000326674	P1	Q9BRB3-2

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70000

AN:

152004

Hom.:

16538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.407

GnomAD3 exomes

AF:

0.487

AC:

119419

AN:

245364

Hom.:

30271

AF XY:

0.486

AC XY:

64883

AN XY:

133370

show subpopulations

Gnomad AFR exome

AF:

0.483

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.616

Gnomad SAS exome

AF:

0.623

Gnomad FIN exome

AF:

0.504

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.429

GnomAD4 exome

AF:

0.447

AC:

650813

AN:

1457106

Hom.:

149486

Cov.:

AF XY:

0.451

AC XY:

326652

AN XY:

724892

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.548

Gnomad4 ASJ exome

AF:

0.377

Gnomad4 EAS exome

AF:

0.666

Gnomad4 SAS exome

AF:

0.620

Gnomad4 FIN exome

AF:

0.510

Gnomad4 NFE exome

AF:

0.420

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.461

AC:

70082

AN:

152120

Hom.:

16570

Cov.:

AF XY:

0.469

AC XY:

34891

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.486

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.376

Gnomad4 EAS

AF:

0.639

Gnomad4 SAS

AF:

0.627

Gnomad4 FIN

AF:

0.506

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.413

Alfa

AF:

0.407

Hom.:

17607

Bravo

AF:

0.453

TwinsUK

AF:

0.404

AC:

1498

ALSPAC

AF:

0.414

AC:

1594

ESP6500AA

AF:

0.479

AC:

2107

ESP6500EA

AF:

0.408

AC:

3507

ExAC

AF:

0.487

AC:

58960

Asia WGS

AF:

0.660

AC:

2296

AN:

3478

EpiCase

AF:

0.393

EpiControl

AF:

0.386

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	GeneDx	Feb 08, 2019	- -

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 71% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 66. Only high quality variants are reported. -

Epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 77

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.020

T;.;.;.;.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.11

T;.;T;T;T;T;T

MetaRNN

Benign

0.000015

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.6

.;N;N;.;.;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.45

PROVEAN

Benign

1.3

N;N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T

Polyphen

0.0, 0.0010

.;B;B;.;.;B;B

Vest4

0.025, 0.024, 0.054, 0.036, 0.053

MPC

0.13

ClinPred

0.010

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.44

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