rs140668735

chr16-578924-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_004204.5(PIGQ):c.1209C>T(p.Tyr403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,608,740 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00049 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (1 hom.)
• Consequence: PIGQ NM_004204.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.561

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 16-578924-C-T is Benign according to our data. Variant chr16-578924-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 456028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-578924-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.561 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000831 (1212/1458640) while in subpopulation NFE AF= 0.001 (1116/1110868). AF 95% confidence interval is 0.000955. There are 1 homozygotes in gnomad4_exome. There are 551 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5	c.1209C>T	p.Tyr403=	synonymous_variant	6/11	ENST00000321878.10
PIGQ	NM_148920.4	c.1209C>T	p.Tyr403=	synonymous_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10	c.1209C>T	p.Tyr403=	synonymous_variant	6/11	1	NM_004204.5	P1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 74 AN: 149990 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000476

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000751

Gnomad OTH AF: 0.00193

GnomAD3 exomes AF: 0.000521 AC: 130 AN: 249682 Hom.: 0 AF XY: 0.000488 AC XY: 66 AN XY: 135352

Gnomad AFR exome AF: 0.000433

Gnomad AMR exome AF: 0.000984

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000735

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000831 AC: 1212 AN: 1458640 Hom.: 1 Cov.: 33 AF XY: 0.000759 AC XY: 551 AN XY: 725688

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000873

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.0000386

Gnomad4 NFE exome AF: 0.00100

Gnomad4 OTH exome AF: 0.000680

GnomAD4 genome AF: 0.000493 AC: 74 AN: 150100 Hom.: 1 Cov.: 33 AF XY: 0.000465 AC XY: 34 AN XY: 73112

Gnomad4 AFR AF: 0.000269

Gnomad4 AMR AF: 0.000475

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000751

Gnomad4 OTH AF: 0.00192

Alfa AF: 0.000692 Hom.: 0

Bravo AF: 0.000665

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PIGQ-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

PIGQ: BP4, BP7 -

Epilepsy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.49
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs140668735; hg19: chr16-628924;