rs75952679

chr16-576227-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004204.5(PIGQ):c.915G>C(p.Leu305=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 1,552,642 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (297 hom., cov: 34)
  • Exomes 𝑓: 0.0051 (233 hom.)
• Consequence: PIGQ NM_004204.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.81

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 16-576227-G-C is Benign according to our data. Variant chr16-576227-G-C is described in ClinVar as [Benign]. Clinvar id is 456055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5	c.915G>C	p.Leu305=	synonymous_variant	4/11	ENST00000321878.10
PIGQ	NM_148920.4	c.915G>C	p.Leu305=	synonymous_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10	c.915G>C	p.Leu305=	synonymous_variant	4/11	1	NM_004204.5	P1

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5166 AN: 152226 Hom.: 294 Cov.: 34

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.0253

GnomAD3 exomes AF: 0.00913 AC: 1427 AN: 156338 Hom.: 57 AF XY: 0.00670 AC XY: 553 AN XY: 82594

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00809

Gnomad ASJ exome AF: 0.00307

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.000331

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.00613

GnomAD4 exome AF: 0.00511 AC: 7158 AN: 1400298 Hom.: 233 Cov.: 34 AF XY: 0.00465 AC XY: 3214 AN XY: 690960

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.00926

Gnomad4 ASJ exome AF: 0.00246

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000541

Gnomad4 FIN exome AF: 0.000188

Gnomad4 NFE exome AF: 0.00225

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0341 AC: 5188 AN: 152344 Hom.: 297 Cov.: 34 AF XY: 0.0336 AC XY: 2506 AN XY: 74492

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00284

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0110 Hom.: 20

Bravo AF: 0.0380

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	8.2
Dann	Benign	0.30

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: rs75952679; hg19: chr16-626227;