chr16-572565-A-G

Variant names:

• chr16-572565-A-G
• rs12917944
• NM_004204.5:c.-9-1501A>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.-9-1501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 455,356 control chromosomes in the GnomAD database, including 53,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16187 hom., cov: 33)
  • Exomes 𝑓: 0.48 (36837 hom.)
• Consequence: PIGQ NM_004204.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0170

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]

ENSG00000282907 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-572565-A-G is Benign according to our data. Variant chr16-572565-A-G is described in ClinVar as [Benign]. Clinvar id is 1185510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGQ	NM_004204.5	c.-9-1501A>G		intron_variant	Intron 1 of 10	ENST00000321878.10	NP_004195.2
PIGQ	NM_148920.4	c.-9-1501A>G		intron_variant	Intron 1 of 9		NP_683721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10	c.-9-1501A>G		intron_variant	Intron 1 of 10	1	NM_004204.5	ENSP00000326674.6

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69171 AN: 151308 Hom.: 16155 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.495 AC: 63591 AN: 128376 Hom.: 16495 AF XY: 0.500 AC XY: 35130 AN XY: 70298

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.547

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.614

Gnomad SAS exome AF: 0.622

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.482 AC: 146510 AN: 303930 Hom.: 36837 Cov.: 0 AF XY: 0.493 AC XY: 85379 AN XY: 173046

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.457 AC: 69255 AN: 151426 Hom.: 16187 Cov.: 33 AF XY: 0.466 AC XY: 34492 AN XY: 73998

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.412

Alfa AF: 0.425 Hom.: 2492

Bravo AF: 0.450

Asia WGS AF: 0.661 AC: 2297 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 71% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 66. Only high quality variants are reported. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Developmental and epileptic encephalopathy, 77 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12917944; hg19: chr16-622565;