rs117537178

Positions:

• chr16-582284-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004204.5(PIGQ):​c.1568G>A​(p.Gly523Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00184 in 1,603,782 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (37 hom.)
• Consequence: PIGQ NM_004204.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.02

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068854094).
• BP6: Variant 16-582284-G-A is Benign according to our data. Variant chr16-582284-G-A is described in ClinVar as [Benign]. Clinvar id is 456036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00312 (476/152350) while in subpopulation AMR AF= 0.0223 (341/15310). AF 95% confidence interval is 0.0203. There are 13 homozygotes in gnomad4. There are 274 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGQ	NM_004204.5	c.1568G>A	p.Gly523Asp	missense_variant	10/11	ENST00000321878.10	NP_004195.2
PIGQ	NM_148920.4	c.1532-599G>A		intron_variant			NP_683721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10	c.1568G>A	p.Gly523Asp	missense_variant	10/11	1	NM_004204.5	ENSP00000326674.6

Frequencies

GnomAD3 genomes AF: 0.00310 AC: 472 AN: 152232 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00576 AC: 1381 AN: 239624 Hom.: 22 AF XY: 0.00570 AC XY: 745 AN XY: 130800

Gnomad AFR exome AF: 0.000390

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00471

Gnomad SAS exome AF: 0.0154

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000466

Gnomad OTH exome AF: 0.00461

GnomAD4 exome AF: 0.00171 AC: 2480 AN: 1451432 Hom.: 37 Cov.: 31 AF XY: 0.00201 AC XY: 1446 AN XY: 720636

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.0223

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00277

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000163

Gnomad4 OTH exome AF: 0.00207

GnomAD4 genome AF: 0.00312 AC: 476 AN: 152350 Hom.: 13 Cov.: 33 AF XY: 0.00368 AC XY: 274 AN XY: 74502

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.0163

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.000433 Hom.: 0

Bravo AF: 0.00413

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00521 AC: 629

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PIGQ-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 17, 2019

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). -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	.;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.64	.;T;T
MetaRNN	Benign	0.0069	T;T;T
MetaSVM	Benign	-0.93	T
PROVEAN	Benign	-0.99	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.42	T;T;T
Sift4G	Uncertain	0.050	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.40
MVP		0.55
ClinPred		0.037	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs117537178; hg19: chr16-632284; COSMIC: COSV50320204; COSMIC: COSV50320204;