rs200388707

chr16-574396-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004204.5(PIGQ):c.322G>A(p.Glu108Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000808 in 1,610,524 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (7 hom., cov: 34)
  • Exomes 𝑓: 0.00081 (16 hom.)
• Consequence: PIGQ NM_004204.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005073428).
• BP6: Variant 16-574396-G-A is Benign according to our data. Variant chr16-574396-G-A is described in ClinVar as [Benign]. Clinvar id is 456044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000834 (127/152286) while in subpopulation SAS AF= 0.0137 (66/4820). AF 95% confidence interval is 0.011. There are 7 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5	c.322G>A	p.Glu108Lys	missense_variant	2/11	ENST00000321878.10
PIGQ	NM_148920.4	c.322G>A	p.Glu108Lys	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10	c.322G>A	p.Glu108Lys	missense_variant	2/11	1	NM_004204.5	P1

Frequencies

GnomAD3 genomes AF: 0.000841 AC: 128 AN: 152168 Hom.: 7 Cov.: 34

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00200 AC: 477 AN: 238602 Hom.: 9 AF XY: 0.00240 AC XY: 313 AN XY: 130466

Gnomad AFR exome AF: 0.000266

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00475

Gnomad SAS exome AF: 0.0124

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000754

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.000806 AC: 1175 AN: 1458238 Hom.: 16 Cov.: 39 AF XY: 0.00108 AC XY: 780 AN XY: 725340

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00280

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152286 Hom.: 7 Cov.: 34 AF XY: 0.000927 AC XY: 69 AN XY: 74458

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000892 Hom.: 0

Bravo AF: 0.000404

ExAC AF: 0.00203 AC: 246

Asia WGS AF: 0.0110 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	13
Dann	Benign	0.76
DEOGEN2	Benign	0.0066	T;.;.;.;.;T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.74	T;.;T;T;T;T;T
MetaRNN	Benign	0.0051	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0, 0.014, 0.0040	.;B;B;.;.;B;B
Vest4		0.083, 0.081, 0.055, 0.077, 0.063
MVP		0.32
MPC		0.15
ClinPred		0.0052	T
GERP RS		2.2
Varity_R		0.022
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs200388707; hg19: chr16-624396; COSMIC: COSV50320926; COSMIC: COSV50320926;