rs200388707

Variant names:

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.322G>A(p.Glu108Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000808 in 1,610,524 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 7 hom., cov: 34)

Exomes 𝑓: 0.00081 ( 16 hom. )

Consequence

PIGQ
NM_004204.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.60

Publications

1 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: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, 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=0.005073428).

BP6

Variant 16-574396-G-A is Benign according to our data. Variant chr16-574396-G-A is described in ClinVar as Benign. ClinVar VariationId is 456044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000834 (127/152286) while in subpopulation SAS AF = 0.0137 (66/4820). AF 95% confidence interval is 0.011. There are 7 homozygotes in GnomAd4. There are 69 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004204.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	NM_004204.5	MANE Select	c.322G>A	p.Glu108Lys	missense	Exon 2 of 11	NP_004195.2
	PIGQ	NM_148920.4		c.322G>A	p.Glu108Lys	missense	Exon 2 of 10	NP_683721.1	Q9BRB3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIGQ	ENST00000321878.10	TSL:1 MANE Select	c.322G>A	p.Glu108Lys	missense	Exon 2 of 11	ENSP00000326674.6	Q9BRB3-2
PIGQ	ENST00000026218.9	TSL:1	c.322G>A	p.Glu108Lys	missense	Exon 2 of 10	ENSP00000026218.5	Q9BRB3-1
PIGQ	ENST00000470411.2	TSL:1	c.322G>A	p.Glu108Lys	missense	Exon 2 of 3	ENSP00000439650.1	Q9BRB3-3

Frequencies

GnomAD3 genomes

AF:

0.000841

AC:

128

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00200

AC:

477

AN:

238602

AF XY:

0.00240

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00475

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000754

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000806

AC:

1175

AN:

1458238

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

780

AN XY:

725340

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44432

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26008

East Asian (EAS)

AF:

0.00280

AC:

111

AN:

39630

South Asian (SAS)

AF:

0.0109

AC:

935

AN:

85842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51644

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1111264

Other (OTH)

AF:

0.00135

AC:

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

187

280

374

467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000834

AC:

127

AN:

152286

Hom.:

Cov.:

AF XY:

0.000927

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41558

American (AMR)

AF:

0.000784

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00521

AC:

AN:

5182

South Asian (SAS)

AF:

0.0137

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68006

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000892

Hom.:

Bravo

AF:

0.000404

ExAC

AF:

0.00203

AC:

246

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy, 77 (1)

Epilepsy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

PhyloP100

1.6

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.083

MVP

0.32

MPC

0.15

ClinPred

0.0052

GERP RS

2.2

Varity_R

0.022

gMVP

0.25

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over