rs2071979

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T14M) has been classified as Likely benign.

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

Publications

44 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 77
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PIGQ links:

ENSG00000282907 (HGNC:):

ENSG00000282907 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PIGQ	NM_004204.5 link	c.40A>G	p.Thr14Ala	missense_variant	Exon 2 of 11	ENST00000321878.10	NP_004195.2	Q9BRB3-2B2RAU6
PIGQ	NM_148920.4 link	c.40A>G	p.Thr14Ala	missense_variant	Exon 2 of 10		NP_683721.1	Q9BRB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10 link	c.40A>G	p.Thr14Ala	missense_variant	Exon 2 of 11	1	NM_004204.5	ENSP00000326674.6		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

GnomAD2 exomes

AF:

0.487

AC:

119419

AN:

245364

AF XY:

0.486

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 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

African (AFR)

AF:

0.487

AC:

16284

AN:

33436

American (AMR)

AF:

0.548

AC:

24433

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9822

AN:

26068

East Asian (EAS)

AF:

0.666

AC:

26412

AN:

39638

South Asian (SAS)

AF:

0.620

AC:

53435

AN:

86138

European-Finnish (FIN)

AF:

0.510

AC:

25773

AN:

50522

Middle Eastern (MID)

AF:

0.328

AC:

1887

AN:

5760

European-Non Finnish (NFE)

AF:

0.420

AC:

466090

AN:

1110722

Other (OTH)

AF:

0.443

AC:

26677

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

19844

39688

59533

79377

99221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14594

29188

43782

58376

72970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.461

AC:

70082

AN:

152120

Hom.:

16570

Cov.:

AF XY:

0.469

AC XY:

34891

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.486

AC:

20170

AN:

41504

American (AMR)

AF:

0.480

AC:

7345

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1304

AN:

3472

East Asian (EAS)

AF:

0.639

AC:

3306

AN:

5172

South Asian (SAS)

AF:

0.627

AC:

3028

AN:

4832

European-Finnish (FIN)

AF:

0.506

AC:

5360

AN:

10584

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28254

AN:

67944

Other (OTH)

AF:

0.413

AC:

874

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1994

3988

5982

7976

9970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.419

Hom.:

28189

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

Feb 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 77

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

5.6

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over