NM_004204.5:c.849G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004204.5(PIGQ):c.849G>T(p.Leu283Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000831 in 1,549,180 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L283L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00052 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00087 ( 18 hom. )

Consequence

PIGQ
NM_004204.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.62

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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-576161-G-T is Benign according to our data. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-576161-G-T is described in CliVar as Benign. Clinvar id is 526294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.62 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000519 (79/152344) while in subpopulation SAS AF = 0.0149 (72/4830). AF 95% confidence interval is 0.0121. There are 1 homozygotes in GnomAd4. There are 58 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 18 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGQ	NM_004204.5 link	c.849G>T	p.Leu283Leu	synonymous_variant	Exon 4 of 11	ENST00000321878.10	NP_004195.2	Q9BRB3-2B2RAU6
PIGQ	NM_148920.4 link	c.849G>T	p.Leu283Leu	synonymous_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.849G>T	p.Leu283Leu	synonymous_variant	Exon 4 of 11	1	NM_004204.5	ENSP00000326674.6		Q9BRB3-2

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00212

AC:

326

AN:

153650

AF XY:

0.00306

show subpopulations

Gnomad AFR exome

AF:

0.000230

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:

0.0000678

Gnomad OTH exome

AF:

0.000913

GnomAD4 exome

AF:

0.000866

AC:

1209

AN:

1396836

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

863

AN XY:

688998

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31616

American (AMR)

AF:

0.00

AC:

AN:

35710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25166

East Asian (EAS)

AF:

0.00

AC:

AN:

35750

South Asian (SAS)

AF:

0.0138

AC:

1095

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46842

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

1078864

Other (OTH)

AF:

0.00104

AC:

AN:

57968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.000519

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41578

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0149

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.0000670

Hom.:

Bravo

AF:

0.000117

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PIGQ: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

PIGQ-related disorder

Benign:1

Nov 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epilepsy

Benign:1

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.64

(source)

DANN

Benign

0.41

PhyloP100

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over