rs145216283

Positions:

chr16-576237-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004204.5(PIGQ):c.925C>G(p.Leu309Val) variant causes a missense change. The variant allele was found at a frequency of 0.00183 in 1,554,050 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0019 ( 3 hom. )

Consequence

PIGQ
NM_004204.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.79

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 links:

ENSG00000282907 (HGNC:):

ENSG00000282907 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017574817).

BP6

Variant 16-576237-C-G is Benign according to our data. Variant chr16-576237-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 526287.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 = 0.000991 (151/152366) while in subpopulation NFE AF= 0.00179 (122/68028). AF 95% confidence interval is 0.00153. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGQ	NM_004204.5 linkuse as main transcript	c.925C>G	p.Leu309Val	missense_variant	4/11	ENST00000321878.10	NP_004195.2	Q9BRB3-2B2RAU6
PIGQ	NM_148920.4 linkuse as main transcript	c.925C>G	p.Leu309Val	missense_variant	4/10		NP_683721.1	Q9BRB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10 linkuse as main transcript	c.925C>G	p.Leu309Val	missense_variant	4/11	1	NM_004204.5	ENSP00000326674.6		Q9BRB3-2

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00109

AC:

172

AN:

157760

Hom.:

AF XY:

0.00111

AC XY:

AN XY:

83504

show subpopulations

Gnomad AFR exome

AF:

0.000654

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000692

Gnomad FIN exome

AF:

0.000726

Gnomad NFE exome

AF:

0.00180

Gnomad OTH exome

AF:

0.000678

GnomAD4 exome

AF:

0.00192

AC:

2686

AN:

1401684

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1268

AN XY:

691786

show subpopulations

Gnomad4 AFR exome

AF:

0.000282

Gnomad4 AMR exome

AF:

0.000386

Gnomad4 ASJ exome

AF:

0.00147

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000679

Gnomad4 FIN exome

AF:

0.000440

Gnomad4 NFE exome

AF:

0.00230

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.000991

AC:

151

AN:

152366

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000700

AC:

ESP6500EA

AF:

0.00142

AC:

ExAC

AF:

0.000697

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	PIGQ: BP4 -

PIGQ-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2022

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

Epilepsy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

.;.;.;T

Eigen

Benign

0.072

Eigen_PC

Benign

0.072

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;D;D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.4

L;L;.;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.82

N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.17

T;T;D;T

Sift4G

Benign

0.20

T;T;D;T

Polyphen

0.75

P;P;.;P

Vest4

0.61

MVP

0.63

MPC

0.41

ClinPred

0.024

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over