NM_004204.5:c.429G>A

Variant names:

• chr16-574503-G-A
• rs33997204
• NM_004204.5:c.429G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_004204.5(PIGQ):​c.429G>A​(p.Leu143Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,607,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: PIGQ NM_004204.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.27
• Publications: 1 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: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282907 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-574503-G-A is Benign according to our data. Variant chr16-574503-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 526285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000201 (293/1455314) while in subpopulation MID AF = 0.00264 (15/5688). AF 95% confidence interval is 0.00162. There are 0 homozygotes in GnomAdExome4. There are 152 alleles in the male GnomAdExome4 subpopulation. Median coverage is 40. This position passed quality control check.

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.429G>A	p.Leu143Leu	synonymous	Exon 2 of 11	NP_004195.2
	PIGQ	NM_148920.4		c.429G>A	p.Leu143Leu	synonymous	Exon 2 of 10	NP_683721.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	ENST00000321878.10	TSL:1 MANE Select	c.429G>A	p.Leu143Leu	synonymous	Exon 2 of 11	ENSP00000326674.6
	PIGQ	ENST00000026218.9	TSL:1	c.429G>A	p.Leu143Leu	synonymous	Exon 2 of 10	ENSP00000026218.5
	PIGQ	ENST00000470411.2	TSL:1	c.429G>A	p.Leu143Leu	synonymous	Exon 2 of 3	ENSP00000439650.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152188 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000258 AC: 60 AN: 232620 AF XY: 0.000243

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000179

Gnomad ASJ exome AF: 0.000727

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000510

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.000876

GnomAD4 exome AF: 0.000201 AC: 293 AN: 1455314 Hom.: 0 Cov.: 40 AF XY: 0.000210 AC XY: 152 AN XY: 723536

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.000158 AC: 7 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.000808 AC: 21 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.0000469 AC: 4 AN: 85342

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51166

Middle Eastern (MID) AF: 0.00264 AC: 15 AN: 5688

European-Non Finnish (NFE) AF: 0.000206 AC: 229 AN: 1109904

Other (OTH) AF: 0.000266 AC: 16 AN: 60096

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152306 Hom.: 0 Cov.: 34 AF XY: 0.000175 AC XY: 13 AN XY: 74472

African (AFR) AF: 0.0000481 AC: 2 AN: 41568

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68008

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000282 Hom.: 0

Bravo AF: 0.000215

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Epilepsy (1)
-	-	1	PIGQ-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0070
DANN	Benign	0.52
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism

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: rs33997204; hg19: chr16-624503;