chr16-574424-C-T

Position:

chr16-574424-C-T

Variant summary

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

The NM_004204.5(PIGQ):c.350C>T(p.Ala117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,610,296 control chromosomes in the GnomAD database, including 46 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0071 ( 43 hom. )

Consequence

PIGQ
NM_004204.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.986

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=0.0066652894).

BP6

Variant 16-574424-C-T is Benign according to our data. Variant chr16-574424-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 456046.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 = 0.00488 (743/152322) while in subpopulation NFE AF= 0.00853 (580/68008). AF 95% confidence interval is 0.00795. There are 3 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 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.350C>T	p.Ala117Val	missense_variant	2/11	ENST00000321878.10	NP_004195.2	Q9BRB3-2B2RAU6
PIGQ	NM_148920.4 linkuse as main transcript	c.350C>T	p.Ala117Val	missense_variant	2/10		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.350C>T	p.Ala117Val	missense_variant	2/11	1	NM_004204.5	ENSP00000326674.6		Q9BRB3-2

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

743

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00395

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00409

AC:

979

AN:

239530

Hom.:

AF XY:

0.00421

AC XY:

551

AN XY:

130858

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.000719

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000401

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.00750

Gnomad OTH exome

AF:

0.00290

GnomAD4 exome

AF:

0.00707

AC:

10312

AN:

1457974

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

4961

AN XY:

725108

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.000807

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000361

Gnomad4 FIN exome

AF:

0.00360

Gnomad4 NFE exome

AF:

0.00867

Gnomad4 OTH exome

AF:

0.00531

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152322

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00395

Gnomad4 NFE

AF:

0.00853

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00714

Hom.:

Bravo

AF:

0.00491

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00722

AC:

ExAC

AF:

0.00380

AC:

460

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	PIGQ: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

PIGQ-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2024

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Developmental and epileptic encephalopathy, 77

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Apr 29, 2022

PIGQ NM_004204.3 exon 2 p.Ala117Val (c.350C>T): This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.8% (580/68016) including 2 homozygotes (https://gnomad.broadinstitute.org/variant/16-574424-C-T?dataset=gnomad_r3). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. This variant is present in ClinVar (Variation ID:456046). In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.24

DANN

Benign

0.92

DEOGEN2

Benign

0.012

T;.;.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.35

T;.;T;T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0067

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N;.;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.67

N;N;N;N;N;N

REVEL

Benign

0.025

Sift

Benign

0.29

T;T;T;T;T;T

Sift4G

Benign

0.23

T;T;T;T;T;T

Polyphen

0.0, 0.0020, 0.0010

.;B;B;.;B;B

Vest4

0.11, 0.11, 0.12, 0.092, 0.11

MVP

0.31

MPC

0.13

ClinPred

0.0029

GERP RS

0.030

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.17

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

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