rs710924

Positions:

• chr16-583353-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000026218.9(PIGQ):​c.2002T>C​(p.Cys668Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,611,930 control chromosomes in the GnomAD database, including 166,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C668Y) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.46 (16177 hom., cov: 33)
  • Exomes 𝑓: 0.45 (150678 hom.)
• Consequence: PIGQ ENST00000026218.9 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.912361E-6).
• BP6: Variant 16-583353-T-C is Benign according to our data. Variant chr16-583353-T-C is described in ClinVar as [Benign]. Clinvar id is 1277846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGQ	NM_004204.5	c.*318T>C		3_prime_UTR_variant	11/11	ENST00000321878.10	NP_004195.2
PIGQ	NM_148920.4	c.2002T>C	p.Cys668Arg	missense_variant	10/10		NP_683721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10	c.*318T>C		3_prime_UTR_variant	11/11	1	NM_004204.5	ENSP00000326674	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69176 AN: 151462 Hom.: 16148 Cov.: 33

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.404

GnomAD3 exomes AF: 0.488 AC: 121834 AN: 249866 Hom.: 30899 AF XY: 0.487 AC XY: 66023 AN XY: 135492

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.617

Gnomad SAS exome AF: 0.624

Gnomad FIN exome AF: 0.507

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.433

GnomAD4 exome AF: 0.448 AC: 654291 AN: 1460354 Hom.: 150678 Cov.: 58 AF XY: 0.452 AC XY: 328380 AN XY: 726506

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.457 AC: 69256 AN: 151576 Hom.: 16177 Cov.: 33 AF XY: 0.465 AC XY: 34447 AN XY: 74048

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.411

Alfa AF: 0.427 Hom.: 6794

Bravo AF: 0.451

TwinsUK AF: 0.399 AC: 1479

ALSPAC AF: 0.414 AC: 1594

ESP6500AA AF: 0.447 AC: 1968

ESP6500EA AF: 0.390 AC: 3354

ExAC AF: 0.489 AC: 59291

Asia WGS AF: 0.658 AC: 2291 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.388

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 72% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 67. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.49
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0000069	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.015
MPC		0.24
ClinPred		0.0069	T
GERP RS		1.3
Varity_R		0.48
gMVP		0.024

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs710924; hg19: chr16-633353; COSMIC: COSV50313344; COSMIC: COSV50313344;