rs141040910

chr16-582906-C-T

Variant summary

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

The ENST00000026218.9(PIGQ):c.1555C>T(p.Arg519Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000807 in 1,609,180 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R519H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (3 hom.)
• Consequence: PIGQ ENST00000026218.9 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.00

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=0.0036675036).
• BP6: Variant 16-582906-C-T is Benign according to our data. Variant chr16-582906-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 456037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00407 (619/152230) while in subpopulation AFR AF= 0.0136 (566/41526). AF 95% confidence interval is 0.0127. There are 5 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5	c.1617C>T	p.Arg539=	synonymous_variant	11/11	ENST00000321878.10
PIGQ	NM_148920.4	c.1555C>T	p.Arg519Cys	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10	c.1617C>T	p.Arg539=	synonymous_variant	11/11	1	NM_004204.5	P1

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 618 AN: 152112 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00122 AC: 303 AN: 249194 Hom.: 1 AF XY: 0.000868 AC XY: 117 AN XY: 134716

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000467 AC: 680 AN: 1456950 Hom.: 3 Cov.: 33 AF XY: 0.000369 AC XY: 267 AN XY: 724232

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.000830

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000622

Gnomad4 OTH exome AF: 0.000914

GnomAD4 genome AF: 0.00407 AC: 619 AN: 152230 Hom.: 5 Cov.: 33 AF XY: 0.00395 AC XY: 294 AN XY: 74430

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00187 Hom.: 1

Bravo AF: 0.00496

ESP6500AA AF: 0.0168 AC: 74

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00146 AC: 177

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

PIGQ: BP4 -

Epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	1.4
Dann	Benign	0.97
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		0.0050	B
Vest4		0.10
MVP		0.21
MPC		0.32
ClinPred		0.020	T
GERP RS		-6.6
Varity_R		0.10
gMVP		0.70

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: rs141040910; hg19: chr16-632906; COSMIC: COSV50314158; COSMIC: COSV50314158;