chr16-576204-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004204.5(PIGQ):c.892G>T(p.Gly298Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G298R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIGQ
NM_004204.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27126855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGQ	NM_004204.5 link	c.892G>T	p.Gly298Trp	missense_variant	Exon 4 of 11	ENST00000321878.10	NP_004195.2	Q9BRB3-2B2RAU6
PIGQ	NM_148920.4 link	c.892G>T	p.Gly298Trp	missense_variant	Exon 4 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.892G>T	p.Gly298Trp	missense_variant	Exon 4 of 11	1	NM_004204.5	ENSP00000326674.6		Q9BRB3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

154298

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398098

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31664

American (AMR)

AF:

0.00

AC:

AN:

35794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35830

South Asian (SAS)

AF:

0.00

AC:

AN:

79280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1079188

Other (OTH)

AF:

0.0000172

AC:

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epilepsy

Uncertain:1

Apr 23, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant has not been reported in the literature in individuals affected with PIGQ-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 298 of the PIGQ protein (p.Gly298Trp). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.057

.;.;.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

.;D;D;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

N;N;.;N

PhyloP100

1.4

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

N;N;D;N

REVEL

Benign

0.16

Sift

Benign

0.063

T;T;D;D

Sift4G

Uncertain

0.029

D;D;D;D

Polyphen

0.20

B;B;.;D

Vest4

0.45

MutPred

0.69

Loss of loop (P = 0.0145);Loss of loop (P = 0.0145);Loss of loop (P = 0.0145);Loss of loop (P = 0.0145);

MVP

0.41

MPC

0.42

ClinPred

0.92

GERP RS

-2.4

Varity_R

0.042

gMVP

0.38

Mutation Taster

=89/11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over