16-576214-G-T

Variant names:

• chr16-576214-G-T
• rs371210440
• NM_004204.5:c.902G>T

Variant summary

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

The NM_004204.5(PIGQ):​c.902G>T​(p.Arg301Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,550,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R301C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: PIGQ NM_004204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• 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: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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=0.2619165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGQ	NM_004204.5	c.902G>T	p.Arg301Leu	missense_variant	Exon 4 of 11	ENST00000321878.10	NP_004195.2
PIGQ	NM_148920.4	c.902G>T	p.Arg301Leu	missense_variant	Exon 4 of 10		NP_683721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10	c.902G>T	p.Arg301Leu	missense_variant	Exon 4 of 11	1	NM_004204.5	ENSP00000326674.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000172 AC: 24 AN: 1398532 Hom.: 0 Cov.: 34 AF XY: 0.0000174 AC XY: 12 AN XY: 689964

African (AFR) AF: 0.00 AC: 0 AN: 31690

American (AMR) AF: 0.00 AC: 0 AN: 35848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35922

South Asian (SAS) AF: 0.00 AC: 0 AN: 79316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 0.0000204 AC: 22 AN: 1079398

Other (OTH) AF: 0.0000345 AC: 2 AN: 58018

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.038	.;.;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	.;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;N;.;N
PhyloP100		1.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;N;D;N
REVEL	Benign	0.070
Sift	Benign	0.25	T;T;D;T
Sift4G	Benign	0.51	T;T;D;T
Polyphen		0.052	B;B;.;P
Vest4		0.49
MutPred		0.70		Loss of methylation at R301 (P = 0.0216);Loss of methylation at R301 (P = 0.0216);Loss of methylation at R301 (P = 0.0216);Loss of methylation at R301 (P = 0.0216);
MVP		0.58
MPC		0.18
ClinPred		0.20	T
GERP RS		1.8
Varity_R		0.054
gMVP		0.42
Mutation Taster		=73/27	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: rs371210440; hg19: chr16-626214;