rs1555451827

Variant names:

• chr16-574687-G-T
• rs1555451827
• NM_004204.5:c.613G>T
• PIGQ p.Ala205Ser

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004204.5(PIGQ):​c.613G>T​(p.Ala205Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,451,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PIGQ NM_004204.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.674
• Publications: 0 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: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282907 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1832771).

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.613G>T	p.Ala205Ser	missense	Exon 2 of 11	NP_004195.2
	PIGQ	NM_148920.4		c.613G>T	p.Ala205Ser	missense	Exon 2 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.613G>T	p.Ala205Ser	missense	Exon 2 of 11	ENSP00000326674.6	Q9BRB3-2
	PIGQ	ENST00000026218.9	TSL:1	c.613G>T	p.Ala205Ser	missense	Exon 2 of 10	ENSP00000026218.5	Q9BRB3-1
	PIGQ	ENST00000470411.2	TSL:1	c.613G>T	p.Ala205Ser	missense	Exon 2 of 3	ENSP00000439650.1	Q9BRB3-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000173 AC: 4 AN: 231018 AF XY: 0.0000235

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000228

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1451610 Hom.: 0 Cov.: 39 AF XY: 0.00000415 AC XY: 3 AN XY: 722168

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46522

Middle Eastern (MID) AF: 0.000204 AC: 1 AN: 4890

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110812

Other (OTH) AF: 0.0000333 AC: 2 AN: 60088

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Epilepsy (1)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	0.071
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.67
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.057
Sift	Benign	0.064	T
Sift4G	Benign	0.079	T
Varity_R		0.045
gMVP		0.31
Mutation Taster		=95/5	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1555451827;

hg19: chr16-624687;