chr16-580902-C-G

Variant names:

• chr16-580902-C-G
• rs1045274
• NM_004204.5:c.1461C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004204.5(PIGQ):​c.1461C>G​(p.Leu487Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,602,088 control chromosomes in the GnomAD database, including 28,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L487L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.17 (2298 hom., cov: 33)
  • Exomes 𝑓: 0.19 (26562 hom.)
• Consequence: PIGQ NM_004204.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.32
• Publications: 20 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: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 16-580902-C-G is Benign according to our data. Variant chr16-580902-C-G is described in ClinVar as Benign. ClinVar VariationId is 1164855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	NM_004204.5	MANE Select	c.1461C>G	p.Leu487Leu	synonymous	Exon 9 of 11	NP_004195.2
	PIGQ	NM_148920.4		c.1461C>G	p.Leu487Leu	synonymous	Exon 9 of 10	NP_683721.1	Q9BRB3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	ENST00000321878.10	TSL:1 MANE Select	c.1461C>G	p.Leu487Leu	synonymous	Exon 9 of 11	ENSP00000326674.6	Q9BRB3-2
	PIGQ	ENST00000026218.9	TSL:1	c.1461C>G	p.Leu487Leu	synonymous	Exon 9 of 10	ENSP00000026218.5	Q9BRB3-1
	PIGQ	ENST00000854227.1		c.1461C>G	p.Leu487Leu	synonymous	Exon 9 of 12	ENSP00000524286.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25175 AN: 152068 Hom.: 2295 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.160 AC: 40039 AN: 249526 AF XY: 0.169

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.0605

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.0232

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.185 AC: 268764 AN: 1449902 Hom.: 26562 Cov.: 29 AF XY: 0.188 AC XY: 135640 AN XY: 721910

African (AFR) AF: 0.156 AC: 5187 AN: 33308

American (AMR) AF: 0.0644 AC: 2878 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4137 AN: 26096

East Asian (EAS) AF: 0.0449 AC: 1783 AN: 39682

South Asian (SAS) AF: 0.257 AC: 22141 AN: 86084

European-Finnish (FIN) AF: 0.185 AC: 9133 AN: 49476

Middle Eastern (MID) AF: 0.119 AC: 688 AN: 5762

European-Non Finnish (NFE) AF: 0.192 AC: 212365 AN: 1104672

Other (OTH) AF: 0.174 AC: 10452 AN: 60102

GnomAD4 genome AF: 0.166 AC: 25193 AN: 152186 Hom.: 2298 Cov.: 33 AF XY: 0.164 AC XY: 12214 AN XY: 74388

African (AFR) AF: 0.156 AC: 6459 AN: 41524

American (AMR) AF: 0.0989 AC: 1514 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3472

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5168

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10600

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12754 AN: 67982

Other (OTH) AF: 0.129 AC: 272 AN: 2112

Alfa AF: 0.106 Hom.: 233

Bravo AF: 0.155

Asia WGS AF: 0.165 AC: 576 AN: 3478

EpiCase AF: 0.176

EpiControl AF: 0.171

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Developmental and epileptic encephalopathy, 77 (1)
-	-	1	Epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-2.3
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: rs1045274; hg19: chr16-630902; COSMIC: COSV50314019; COSMIC: COSV50314019;