rs144613953

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004204.5(PIGQ):c.1546C>A(p.Arg516Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,607,022 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R516H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0025 ( 12 hom. )

Consequence

PIGQ
NM_004204.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.17

Publications

4 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:

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=0.018725783).

BP6

Variant 16-582262-C-A is Benign according to our data. Variant chr16-582262-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 456035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00131 (200/152362) while in subpopulation NFE AF = 0.00229 (156/68026). AF 95% confidence interval is 0.002. There are 0 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 12 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGQ	NM_004204.5 link	c.1546C>A	p.Arg516Ser	missense_variant	Exon 10 of 11	ENST00000321878.10	NP_004195.2	Q9BRB3-2B2RAU6
PIGQ	NM_148920.4 link	c.1532-621C>A		intron_variant	Intron 9 of 9		NP_683721.1	Q9BRB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10 link	c.1546C>A	p.Arg516Ser	missense_variant	Exon 10 of 11	1	NM_004204.5	ENSP00000326674.6		Q9BRB3-2

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

200

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00159

AC:

379

AN:

239062

AF XY:

0.00164

show subpopulations

Gnomad AFR exome

AF:

0.000264

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.000205

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000253

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00188

GnomAD4 exome

AF:

0.00246

AC:

3572

AN:

1454660

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1745

AN XY:

723146

show subpopulations

African (AFR)

AF:

0.000420

AC:

AN:

33362

American (AMR)

AF:

0.00193

AC:

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.0000769

AC:

AN:

26022

East Asian (EAS)

AF:

0.00

AC:

AN:

39452

South Asian (SAS)

AF:

0.000984

AC:

AN:

85394

European-Finnish (FIN)

AF:

0.000390

AC:

AN:

51344

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00293

AC:

3246

AN:

1108790

Other (OTH)

AF:

0.00188

AC:

113

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

152

305

457

610

762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

256

384

512

640

<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:

0.00131

AC:

200

AN:

152362

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41586

American (AMR)

AF:

0.00157

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00229

AC:

156

AN:

68026

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00210

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00156

AC:

188

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PIGQ: BP4 -

Epilepsy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 77

Benign:1

Jun 07, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

1.2

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.063

T;T;D

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.20

B;B;.

Vest4

0.70

MVP

0.33

ClinPred

0.015

GERP RS

2.8

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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