rs145216283

Positions:

• chr16-576237-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004204.5(PIGQ):​c.925C>G​(p.Leu309Val) variant causes a missense change. The variant allele was found at a frequency of 0.00183 in 1,554,050 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L309L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00099 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0019 (3 hom.)
• Consequence: PIGQ NM_004204.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.79

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017574817).
• BP6: Variant 16-576237-C-G is Benign according to our data. Variant chr16-576237-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 526287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000991 (151/152366) while in subpopulation NFE AF= 0.00179 (122/68028). AF 95% confidence interval is 0.00153. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5	c.925C>G	p.Leu309Val	missense_variant	4/11	ENST00000321878.10
PIGQ	NM_148920.4	c.925C>G	p.Leu309Val	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10	c.925C>G	p.Leu309Val	missense_variant	4/11	1	NM_004204.5	P1

Frequencies

GnomAD3 genomes AF: 0.000992 AC: 151 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00109 AC: 172 AN: 157760 Hom.: 1 AF XY: 0.00111 AC XY: 93 AN XY: 83504

Gnomad AFR exome AF: 0.000654

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000692

Gnomad FIN exome AF: 0.000726

Gnomad NFE exome AF: 0.00180

Gnomad OTH exome AF: 0.000678

GnomAD4 exome AF: 0.00192 AC: 2686 AN: 1401684 Hom.: 3 Cov.: 34 AF XY: 0.00183 AC XY: 1268 AN XY: 691786

Gnomad4 AFR exome AF: 0.000282

Gnomad4 AMR exome AF: 0.000386

Gnomad4 ASJ exome AF: 0.00147

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000679

Gnomad4 FIN exome AF: 0.000440

Gnomad4 NFE exome AF: 0.00230

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.000991 AC: 151 AN: 152366 Hom.: 0 Cov.: 34 AF XY: 0.000953 AC XY: 71 AN XY: 74498

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00114

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000700 AC: 3

ESP6500EA AF: 0.00142 AC: 12

ExAC AF: 0.000697 AC: 77

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PIGQ-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

PIGQ: BP4 -

Epilepsy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	0.072
Eigen_PC	Benign	0.072
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.018	T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.4	L;L;.;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.82	N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.17	T;T;D;T
Sift4G	Benign	0.20	T;T;D;T
Polyphen		0.75	P;P;.;P
Vest4		0.61
MVP		0.63
MPC		0.41
ClinPred		0.024	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.59

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: rs145216283; hg19: chr16-626237;