rs2071979

chr16-574114-A-G

Variant summary

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

The NM_004204.5(PIGQ):c.40A>G(p.Thr14Ala) variant causes a missense change. The variant allele was found at a frequency of 0.448 in 1,609,226 control chromosomes in the GnomAD database, including 166,056 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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. T14M) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.46 (16570 hom., cov: 34)
  • Exomes 𝑓: 0.45 (149486 hom.)
• Consequence: PIGQ NM_004204.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.63

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=1.4899833E-5).
• BP6: Variant 16-574114-A-G is Benign according to our data. Variant chr16-574114-A-G is described in ClinVar as [Benign]. Clinvar id is 1164853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5	c.40A>G	p.Thr14Ala	missense_variant	2/11	ENST00000321878.10
PIGQ	NM_148920.4	c.40A>G	p.Thr14Ala	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10	c.40A>G	p.Thr14Ala	missense_variant	2/11	1	NM_004204.5	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70000 AN: 152004 Hom.: 16538 Cov.: 34

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.407

GnomAD3 exomes AF: 0.487 AC: 119419 AN: 245364 Hom.: 30271 AF XY: 0.486 AC XY: 64883 AN XY: 133370

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.558

Gnomad ASJ exome AF: 0.368

Gnomad EAS exome AF: 0.616

Gnomad SAS exome AF: 0.623

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.447 AC: 650813 AN: 1457106 Hom.: 149486 Cov.: 45 AF XY: 0.451 AC XY: 326652 AN XY: 724892

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.510

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.461 AC: 70082 AN: 152120 Hom.: 16570 Cov.: 34 AF XY: 0.469 AC XY: 34891 AN XY: 74384

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.413

Alfa AF: 0.407 Hom.: 17607

Bravo AF: 0.453

TwinsUK AF: 0.404 AC: 1498

ALSPAC AF: 0.414 AC: 1594

ESP6500AA AF: 0.479 AC: 2107

ESP6500EA AF: 0.408 AC: 3507

ExAC AF: 0.487 AC: 58960

Asia WGS AF: 0.660 AC: 2296 AN: 3478

EpiCase AF: 0.393

EpiControl AF: 0.386

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 08, 2019

- -

Epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 77 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	13
Dann	Benign	0.64
DEOGEN2	Benign	0.020	T;.;.;.;.;T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.11	T;.;T;T;T;T;T
MetaRNN	Benign	0.000015	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.3	N;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;.;.;B;B
Vest4		0.025, 0.024, 0.054, 0.036, 0.053
MPC		0.13
ClinPred		0.010	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.44

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: rs2071979; hg19: chr16-624114; COSMIC: COSV50313601; COSMIC: COSV50313601;