rs1981483

Variant names:

• chr16-580665-G-A
• rs1981483
• NM_004204.5:c.1417-193G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-580665-G-A
• chr16-580665-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004204.5(PIGQ):​c.1417-193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 607,444 control chromosomes in the GnomAD database, including 69,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16813 hom., cov: 33)
  • Exomes 𝑓: 0.47 (52800 hom.)
• Consequence: PIGQ NM_004204.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.49
• Publications: 14 publications found

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]

PIGQ Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 77

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-580665-G-A is Benign according to our data. Variant chr16-580665-G-A is described in ClinVar as Benign. ClinVar VariationId is 1281528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004204.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	NM_004204.5	MANE Select	c.1417-193G>A		intron	N/A	NP_004195.2
	PIGQ	NM_148920.4		c.1417-193G>A		intron	N/A	NP_683721.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	ENST00000321878.10	TSL:1 MANE Select	c.1417-193G>A		intron	N/A	ENSP00000326674.6
	PIGQ	ENST00000026218.9	TSL:1	c.1417-193G>A		intron	N/A	ENSP00000026218.5
	PIGQ	ENST00000480424.6	TSL:2	n.607G>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70516 AN: 151992 Hom.: 16782 Cov.: 33

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.471 AC: 214581 AN: 455334 Hom.: 52800 Cov.: 0 AF XY: 0.478 AC XY: 115436 AN XY: 241248

African (AFR) AF: 0.494 AC: 6334 AN: 12830

American (AMR) AF: 0.523 AC: 10532 AN: 20150

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 5314 AN: 13676

East Asian (EAS) AF: 0.679 AC: 21449 AN: 31606

South Asian (SAS) AF: 0.620 AC: 29419 AN: 47432

European-Finnish (FIN) AF: 0.515 AC: 15641 AN: 30390

Middle Eastern (MID) AF: 0.350 AC: 677 AN: 1934

European-Non Finnish (NFE) AF: 0.419 AC: 113650 AN: 271226

Other (OTH) AF: 0.443 AC: 11565 AN: 26090

GnomAD4 genome AF: 0.464 AC: 70600 AN: 152110 Hom.: 16813 Cov.: 33 AF XY: 0.472 AC XY: 35120 AN XY: 74372

African (AFR) AF: 0.493 AC: 20441 AN: 41474

American (AMR) AF: 0.483 AC: 7391 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1322 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3313 AN: 5170

South Asian (SAS) AF: 0.628 AC: 3035 AN: 4832

European-Finnish (FIN) AF: 0.506 AC: 5365 AN: 10602

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28411 AN: 67946

Other (OTH) AF: 0.418 AC: 883 AN: 2114

Alfa AF: 0.462 Hom.: 2142

Bravo AF: 0.457

Asia WGS AF: 0.662 AC: 2304 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.37
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1981483; hg19: chr16-630665;